Genetically engineered human cortical spheroid models of tuberous sclerosis.

Tuberous sclerosis complex (TSC) is a multisystem developmental disorder caused by mutations in the TSC1 or TSC2 genes, whose protein products are negative regulators of mechanistic target of rapamycin complex 1 signaling. Hallmark pathologies of TSC are cortical tubers-regions of dysmorphic, disorganized neurons and glia in the cortex that are linked to epileptogenesis. To determine the developmental origin of tuber cells, we established human cellular models of TSC by CRISPR-Cas9-mediated gene editing of TSC1 or TSC2 in human pluripotent stem cells (hPSCs). Using heterozygous TSC2 hPSCs with a conditional mutation in the functional allele, we show that mosaic biallelic inactivation during neural progenitor expansion is necessary for the formation of dysplastic cells and increased glia production in three-dimensional cortical spheroids. Our findings provide support for the second-hit model of cortical tuber formation and suggest that variable developmental timing of somatic mutations could contribute to the heterogeneity in the neurological presentation of TSC

B-Physics at the Tevatron (Proceedings of PASCOS2010)

We report on recent B-Physics results from the Tevatron. The topics covered include measurement of the polarization amplitudes in $B_s^0 \to \phi \phi$, the search for rare flavor-changing neutral-current decays, CP violation in $B_s^0 \to J/\psi \phi$ and semileptonic $B_s^0$ decays, and a new measurement of the like-sign asymmetry in dimuon events.Comment: 6 pages, proceedings paper, 16th International Symposium on Particles, Strings, and Cosmology, Valencia, Spain, July 19 - 23, 201

Share Repurchases and Acquisitions: An Analysis of Which Firms Participate

Firms can transmit cash to shareholders either by paying dividends or by purchasing shares. The share purchases can be either the firm's own securities or those of another firm. Recent evidence suggests that there has been a dramatic increase in the use of these nondividend payments to shareholders. This paper reviews the theories which have been offered regarding the motivation of nondividend payments. These include taxation advantages, adjustment towards optimal debt-equity ratios, anti-takeover strategies, free cash flow (agency) considerations, signaling, and habit formation or learning. From these theories, we derive and investigate econometrically potential characteristics which predict participation in the above actions for roughly 2.000 firms in 1976 and 1984. We find the variables suggested by the various hypotheses collectively have substantial power in predicting participation in share repurchase and acquisitions. The free cash flow and habit forming arguments prove most consistent with our findings. Tests for structural change across time confirm an intercept shift consistent with dramatic increases in these activities, and fail to reject that the characteristic determinants of these actions are unchanged.

Parthenolide eliminates leukemia-initiating cell populations and improves survival in xenografts of childhood acute lymphoblastic leukemia

Key Points First report demonstrating in vivo elimination of multiple LIC populations from childhood ALL cases using animal models. In vivo models of leukemia are essential for drug evaluation studies.</jats:p

Executive Orders: Promoting Democracy and Openness in New York State Government

This joint report outlines 11 executive actions Gov. Andrew Cuomo can take to open up New York State government, increase the accountability of state agencies and reduce barriers to voting. The orders are centered on the basic goal of empowering the citizenry with more and better information about what its government is doing, and how it is spending tax payer dollars

A survey of the administration of audio-visual aids departments in the schools of Massachusetts.

Thesis (Ed.M.)--Boston Universit