The competitive NMDA antagonist CPP protects substantia nigra neurons from MPTP-induced degeneration in primates

Degeneration of nigrostriatal dopaminergic neurons is the primary histopathological feature of Parkinson's disease. The neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) induces a neurological syndrome in man and non-human primates very similar to idiopathic Parkinson's disease by selectively destroying dopaminergic nigrostriatal neurons. This gives rise to the hypothesis that Parkinson's disease may be caused by endogenous or environmental toxins. Endogenous excitatory amino acids (EAAs) such as L-glutamate could be involved in neurodegenerative disorders including Parkinson's disease. We report in this study that the competitive NMDA antagonist CPP (3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid) protects nigral tyrosine hydroxylase (TH) positive neurons from degeneration induced by systemic treatment with MPTP in common marmosets. This indicates that EAAs are involved in the pathophysiological cascade of MPTP-induced neuronal cell death and that EAA antagonists may offer a neuroprotective therapy for Parkinson's disease

A graduate level treatment of the design of a machine for the 1999 2.007 contest

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 1999.Includes bibliographical references (p. 359).by Michael P. Schmidt-Lange.S.M

Stubborn Predictions in Primary Visual Cortex

Perceivers can use past experiences to make sense of ambiguous sensory signals. However, this may be inappropriate when the world changes and past experiences no longer predict what the future holds. Optimal learning models propose that observers decide whether to stick with or update their predictions by tracking the uncertainty or "precision" of their expectations. However, contrasting theories of prediction have argued that we are prone to misestimate uncertainty-leading to stubborn predictions that are difficult to dislodge. To compare these possibilities, we had participants learn novel perceptual predictions before using fMRI to record visual brain activity when predictive contingencies were disrupted-meaning that previously "expected" events become objectively improbable. Multivariate pattern analyses revealed that expected events continued to be decoded with greater fidelity from primary visual cortex, despite marked changes in the statistical structure of the environment, which rendered these expectations no longer valid. These results suggest that our perceptual systems do indeed form stubborn predictions even from short periods of learning-and more generally suggest that top-down expectations have the potential to help or hinder perceptual inference in bounded minds like ours

The external benefits of higher education

The private market benefits of education are widely studied at the micro level, although the magnitude of their macroeconomic impact is disputed. However, there are additional benefits of education, which are less well understood. In this paper the macroeconomic effects of external benefits of higher education are estimated using the “micro-to-macro” simulation approach. Two types of externalities are explored: technology spillovers and productivity spillovers in the labour market. These links are illustrated and the results suggest they could be very large. However, this is qualified by the dearth of microeconomic evidence, for which we hope to encourage further work

Observation of vanishing charge dispersion of a nearly-open superconducting island

Isolation from the environment determines the extent to which charge is confined on an island, which manifests as Coulomb oscillations such as charge dispersion. We investigate the charge dispersion of a nanowire transmon hosting a quantum dot in the junction. We observe rapid suppression of the charge dispersion with increasing junction transparency, consistent with the predicted scaling law which incorporates two branches of the Josephson potential. We find improved qubit coherence times at the point of highest suppression, suggesting novel approaches for building charge-insensitive qubits

The impact of changing work schedules on American firefighters’ sleep patterns and well-being

Across the nation, fire departments are adopting the 48/96 work schedule, in which firefighters work 48 consecutive hours with the following 96 hours off. Our study objective was to explain and quantify the impact of switching from the Kelly schedule to the 48/96 schedule by measuring changes in sleep, feelings of daytime function, as well as perceptions of professional and personal well-being for American firefighters. Sleep diaries and self-reported surveys were administered to firefighters at an urban fire department. Sleep diaries measuring the number of hours slept and feelings of refreshment were compared one month before and four months after implementation of the 48/96 schedule. The self-reported surveys measured sleepiness levels via the Epworth Sleepiness Scale. Secondary study objectives included changes in professional and personal well-being time for personal schedules, satisfaction, and health habits before and after the 48/96 schedule was implemented. The 59 firefighters included in the study reported an increase in sleep on-shift after the new schedule implementation (5.8 to 6.6 hours/night, p < 0.001). Participants also reported increased feelings of refreshment on days off (p < 0.001) and decreased daytime sleepiness (p < 0.001). We also found a general trend of improved perceptions of satisfaction, less shift interference with personal schedules and decreased feelings of burnout. American firefighters appeared to benefit from a 48/96 schedule, with short-term improvements in sleep patterns, feelings of burnout, and time for personal schedules

Traditional and Health-Related Philanthropy: The Role of Resources and Personality

I study the relationships of resources and personality characteristics to charitable giving, postmortem organ donation, and blood donation in a nationwide sample of persons in households in the Netherlands. I find that specific personality characteristics are related to specific types of giving: agreeableness to blood donation, empathic concern to charitable giving, and prosocial value orientation to postmortem organ donation. I find that giving has a consistently stronger relation to human and social capital than to personality. Human capital increases giving; social capital increases giving only when it is approved by others. Effects of prosocial personality characteristics decline at higher levels of these characteristics. Effects of empathic concern, helpfulness, and social value orientations on generosity are mediated by verbal proficiency and church attendance.

Probing the Early Stages of Low-Mass Star Formation in LDN 1689N: Dust and Water in IRAS 16293-2422A, B, and E

We present deep images of dust continuum emission at 450, 800, and 850 micron of the dark cloud LDN 1689N which harbors the low-mass young stellar objects (YSOs) IRAS 16293-2422A and B (I16293A and I16293B) and the cold prestellar object I16293E. Toward the positions of I16293A and E we also obtained spectra of CO-isotopomers and deep submillimeter observations of chemically related molecules with high critical densities. To I16293A we report the detection of the HDO 1_01 - 0_00 and H2O 1_10 - 1_01 ground-state transitions as broad self-reversed emission profiles with narrow absorption, and a tentative detection of H2D+ 1_10 - 1_11. To I16293E we detect weak emission of subthermally excited HDO 1_01 - 0_00. Based on this set of submillimeter continuum and line data we model the envelopes around I16293A and E. The density and velocity structure of I16293A is fit by an inside-out collapse model, yielding a sound speed of a=0.7 km/s, an age of t=(0.6--2.5)e4 yr, and a mass of 6.1 Msun. The density in the envelope of I16293E is fit by a radial power law with index -1.0+/-0.2, a mass of 4.4 Msun, and a constant temperature of 16K. These respective models are used to study the chemistry of the envelopes of these pre- and protostellar objects. The [HDO]/[H2O] abundance ratio in the warm inner envelope of I16293A of a few times 1e-4 is comparable to that measured in comets. This supports the idea that the [HDO]/[H2O] ratio is determined in the cold prestellar core phase and conserved throughout the formation process of low-mass stars and planets.Comment: 61 pages, 17 figures. Accepted for publication in ApJ. To get Fig. 13: send email to [email protected]