A Bayesian measurement error model for two-channel cell-based RNAi data with replicates

RNA interference (RNAi) is an endogenous cellular process in which small double-stranded RNAs lead to the destruction of mRNAs with complementary nucleoside sequence. With the production of RNAi libraries, large-scale RNAi screening in human cells can be conducted to identify unknown genes involved in a biological pathway. One challenge researchers face is how to deal with the multiple testing issue and the related false positive rate (FDR) and false negative rate (FNR). This paper proposes a Bayesian hierarchical measurement error model for the analysis of data from a two-channel RNAi high-throughput experiment with replicates, in which both the activity of a particular biological pathway and cell viability are monitored and the goal is to identify short hair-pin RNAs (shRNAs) that affect the pathway activity without affecting cell activity. Simulation studies demonstrate the flexibility and robustness of the Bayesian method and the benefits of having replicates in the experiment. This method is illustrated through analyzing the data from a RNAi high-throughput screening that searches for cellular factors affecting HCV replication without affecting cell viability; comparisons of the results from this HCV study and some of those reported in the literature are included.Comment: Published in at http://dx.doi.org/10.1214/11-AOAS496 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

An SMC-like protein binds and regulates Caenorhabditis elegans condensins

Structural Maintenance of Chromosomes (SMC) family proteins participate in multisubunit complexes that govern chromosome structure and dynamics. SMC-containing condensin complexes create chromosome topologies essential for mitosis/meiosis, gene expression, recombination, and repair. Many eukaryotes have two condensin complexes (I and II); C. elegans has three (I, II, and the X-chromosome specialized condensin IDC) and their regulation is poorly understood. Here we identify a novel SMC-like protein, SMCL-1, that binds to C. elegans condensin SMC subunits, and modulates condensin functions. Consistent with a possible role as a negative regulator, loss of SMCL-1 partially rescued the lethal and sterile phenotypes of a hypomorphic condensin mutant, while over-expression of SMCL-1 caused lethality, chromosome mis-segregation, and disruption of condensin IDC localization on X chromosomes. Unlike canonical SMC proteins, SMCL-1 lacks hinge and coil domains, and its ATPase domain lacks conserved amino acids required for ATP hydrolysis, leading to the speculation that it may inhibit condensin ATPase activity. SMCL-1 homologs are apparent only in the subset of Caenorhabditis species in which the condensin I and II subunit SMC-4 duplicated to create the condensin IDC- specific subunit DPY-27, suggesting that SMCL-1 helps this lineage cope with the regulatory challenges imposed by evolution of a third condensin complex. Our findings uncover a new regulator of condensins and highlight how the duplication and divergence of SMC complex components in various lineages has created new proteins with diverse functions in chromosome dynamics

Metallic helix array as a broadband wave plate

This study proposes that a metallic helix array can operate as a highly-transparent broadband wave plate in propagation directions perpendicular to the axis of helices. The functionality arises from a special property of the helix array, namely that the eigenstates of elliptically right-handed and left-handed polarization are dominated by Bragg scattering and local resonance respectively, and can be modulated separately with nearly fixed difference between their wavevectors in a wide frequency range. The wave plate functionality is theoretically and experimentally demonstrated by the transformation of polarized states in a wide frequency range

Optimal interval and duration of CAM-ICU assessments for delirium detection after cardiac surgery

STUDY OBJECTIVE: Our goal was to determine when postoperative delirium first occurs, and to assess evaluation strategies that reliably detect delirium with lowest frequency of testing. DESIGN: This was a retrospective study that used a database from a five-center randomized trial. SETTING: Postoperative cardiothoracic ICU and surgical wards. PARTICIPANT: Adults scheduled for elective coronary artery bypass and/or valve surgery. INTERVENTION AND MEASUREMENTS: Postoperative delirium was assessed using CAM-ICU questionnaires twice daily for 5 days or until hospital discharge. Data were analyzed using frequency tables and Kaplan-Meier time-to-event estimators, the latter being used to summarize time to first positive CAM-ICU over POD1-5 for all patients for various evaluation strategies, including all assessments, only morning assessment, and only afternoon assessments. Sensitivity for various strategies were compared using McNemar\u27s test for paired proportions. MAIN RESULTS: A total of 95 of 788 patients (12% [95% CI, 10% to 15%]) had at least 1 episode of delirium within the first 5 postoperative days. Among all patients with delirium, 65% were identified by the end of the first postoperative day. Delirium was detected more often in the mornings (10% of patients) than evenings (7% of patients). Compared to delirium assessments twice daily for five days, we found that twice daily assessments for 4 days detected an estimated 97% (95% CI 91%, 99%) of delirium. Measurements twice daily for three days detected 90% (82%, 95%) of delirium. CONCLUSIONS: Postoperative delirium is common, and CAM-ICU assessments twice daily for 4 days, versus 5 days, detects nearly all delirium with 20% fewer assessments. Four days of assessment may usually be sufficient for clinical and research purposes

Trees over Infinite Structures and Path Logics with Synchronization

We provide decidability and undecidability results on the model-checking problem for infinite tree structures. These tree structures are built from sequences of elements of infinite relational structures. More precisely, we deal with the tree iteration of a relational structure M in the sense of Shelah-Stupp. In contrast to classical results where model-checking is shown decidable for MSO-logic, we show decidability of the tree model-checking problem for logics that allow only path quantifiers and chain quantifiers (where chains are subsets of paths), as they appear in branching time logics; however, at the same time the tree is enriched by the equal-level relation (which holds between vertices u, v if they are on the same tree level). We separate cleanly the tree logic from the logic used for expressing properties of the underlying structure M. We illustrate the scope of the decidability results by showing that two slight extensions of the framework lead to undecidability. In particular, this applies to the (stronger) tree iteration in the sense of Muchnik-Walukiewicz.Comment: In Proceedings INFINITY 2011, arXiv:1111.267

Spectral Correlation in Incommensurate Multi-Walled Carbon Nanotubes

We investigate the energy spectra of clean incommensurate double-walled carbon nanotubes, and find that the overall spectral properties are described by the so-called critical statistics of Anderson metal-insulator transition. In the energy spectra, there exist three different regimes characterized by Wigner-Dyson, Poisson, and semi-Poisson distributions. This feature implies that the electron transport in incommensurate multi-walled nanotubes can be either diffusive, ballistic, or intermediate between them, depending on the position of the Fermi energy.Comment: final version to appear in Phys. Rev. Let

Study of the Baryon-Antibaryon Low-Mass Enhancements in Charmless Three-body Baryonic B Decays

The angular distributions of the baryon-antibaryon low-mass enhancements seen in the charmless three-body baryonic B decays B+ -> p pbar K+, B0 -> p pbar Ks, and B0 -> p Lambdabar pi- are reported. A quark fragmentation interpretation is supported, while the gluonic resonance picture is disfavored. Searches for the Theta+ and Theta++ pentaquarks in the relevant decay modes and possible glueball states G with 2.2 GeV/c2 < M-ppbar < 2.4 GeV/c2 in the ppbar systems give null results. We set upper limits on the products of branching fractions, B(B0 -> Theta+ p)\times B(Theta+ -> p Ks) Theta++ pbar) \times B(Theta++ -> p K+) G K+) \times B(G -> p pbar) < 4.1 \times 10^{-7} at the 90% confidence level. The analysis is based on a 140 fb^{-1} data sample recorded on the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric-energy e+e- collider.Comment: 14 pages, 13 figure files, update of hep-ex/0409010 for journal submisssio