On asymptotically optimal tests under loss of identifiability in semiparametric models

We consider tests of hypotheses when the parameters are not identifiable under the null in semiparametric models, where regularity conditions for profile likelihood theory fail. Exponential average tests based on integrated profile likelihood are constructed and shown to be asymptotically optimal under a weighted average power criterion with respect to a prior on the nonidentifiable aspect of the model. These results extend existing results for parametric models, which involve more restrictive assumptions on the form of the alternative than do our results. Moreover, the proposed tests accommodate models with infinite dimensional nuisance parameters which either may not be identifiable or may not be estimable at the usual parametric rate. Examples include tests of the presence of a change-point in the Cox model with current status data and tests of regression parameters in odds-rate models with right censored data. Optimal tests have not previously been studied for these scenarios. We study the asymptotic distribution of the proposed tests under the null, fixed contiguous alternatives and random contiguous alternatives. We also propose a weighted bootstrap procedure for computing the critical values of the test statistics. The optimal tests perform well in simulation studies, where they may exhibit improved power over alternative tests.Comment: Published in at http://dx.doi.org/10.1214/08-AOS643 the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org

Is the worst over? Economic indexes and the course of the recession in New York and New Jersey

The New York-New Jersey region entered a pronounced downturn in 2008, but the pace of decline eased considerably in spring 2009 and then leveled off in July, according to three key Federal Reserve Bank of New York economic indexes. These developments, in conjunction with a growing consensus that the national economy is headed for recovery, suggest that the worst may be over for the region's economy. However, a downsizing of the area's critical finance sector could pose a major risk to the economic outlook going forward--particularly for New York City.Federal Reserve Bank of New York ; Federal Reserve District, 2nd ; Economic conditions ; Economic indicators

Scanning optical homodyne detection of high-frequency picoscale resonances in cantilever and tuning fork sensors

Higher harmonic modes in nanoscale silicon cantilevers and microscale quartz tuning forks are detected and characterized using a custom scanning optical homodyne interferometer. Capable of both mass and force sensing, these resonators exhibit high-frequency harmonic motion content with picometer-scale amplitudes detected in a 2.5 MHz bandwidth, driven by ambient thermal radiation. Quartz tuning forks additionally display both in-plane and out-of-plane harmonics. The first six electronically detected resonances are matched to optically detected and mapped fork eigenmodes. Mass sensing experiments utilizing higher tuning fork modes indicate >6x sensitivity enhancement over fundamental mode operation.Comment: 3 pages, 3 figures, submitted to Applied Physics Letter

Programmable base editing of zebrafish genome using a modified CRISPR-Cas9 system.

Precise genetic modifications in model animals are essential for biomedical research. Here, we report a programmable "base editing" system to induce precise base conversion with high efficiency in zebrafish. Using cytidine deaminase fused to Cas9 nickase, up to 28% of site-specific single-base mutations are achieved in multiple gene loci. In addition, an engineered Cas9-VQR variant with 5'-NGA PAM specificities is used to induce base conversion in zebrafish. This shows that Cas9 variants can be used to expand the utility of this technology. Collectively, the targeted base editing system represents a strategy for precise and effective genome editing in zebrafish.The use of base editing enables precise genetic modifications in model animals. Here the authors show high efficient single-base editing in zebrafish using modified Cas9 and its VQR variant with an altered PAM specificity

Kinetic Approaches to Understanding the Mechanisms of Fidelity of the Herpes Simplex Virus Type 1 DNA Polymerase

We discuss how the results of presteady-state and steady-state kinetic analysis of the polymerizing and excision activities of herpes simplex virus type 1 (HSV-1) DNA polymerase have led to a better understanding of the mechanisms controlling fidelity of this important model replication polymerase. Despite a poorer misincorporation frequency compared to other replicative polymerases with intrinsic 3′ to 5′ exonuclease (exo) activity, HSV-1 DNA replication fidelity is enhanced by a high kinetic barrier to extending a primer/template containing a mismatch or abasic lesion and by the dynamic ability of the polymerase to switch the primer terminus between the exo and polymerizing active sites. The HSV-1 polymerase with a catalytically inactivated exo activity possesses reduced rates of primer switching and fails to support productive replication, suggesting a novel means to target polymerase for replication inhibition