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

Mutations in the PKM2 exon-10 region are associated with reduced allostery and increased nuclear translocation.

PKM2 is a key metabolic enzyme central to glucose metabolism and energy expenditure. Multiple stimuli regulate PKM2's activity through allosteric modulation and post-translational modifications. Furthermore, PKM2 can partner with KDM8, an oncogenic demethylase and enter the nucleus to serve as a HIF1α co-activator. Yet, the mechanistic basis of the exon-10 region in allosteric regulation and nuclear translocation remains unclear. Here, we determined the crystal structures and kinetic coupling constants of exon-10 tumor-related mutants (H391Y and R399E), showing altered structural plasticity and reduced allostery. Immunoprecipitation analysis revealed increased interaction with KDM8 for H391Y, R399E, and G415R. We also found a higher degree of HIF1α-mediated transactivation activity, particularly in the presence of KDM8. Furthermore, overexpression of PKM2 mutants significantly elevated cell growth and migration. Together, PKM2 exon-10 mutations lead to structure-allostery alterations and increased nuclear functions mediated by KDM8 in breast cancer cells. Targeting the PKM2-KDM8 complex may provide a potential therapeutic intervention

Searching for Moving Objects in HSC-SSP: Pipeline and Preliminary Results

The Hyper Suprime-Cam Subaru Strategic Program (HSC-SSP) is currently the deepest wide- field survey in progress. The 8.2 m aperture of Subaru telescope is very powerful in detect- ing faint/small moving objects, including near-Earth objects, asteroids, centaurs and Tran- Neptunian objects (TNOs). However, the cadence and dithering pattern of the HSC-SSP are not designed for detecting moving objects, making it difficult to do so systematically. In this paper, we introduce a new pipeline for detecting moving objects (specifically TNOs) in a non-dedicated survey. The HSC-SSP catalogs are re-arranged into the HEALPix architecture. Then, the stationary detections and false positive are removed with a machine learning al- gorithm to produce a list of moving object candidates. An orbit linking algorithm and visual inspections are executed to generate the final list of detected TNOs. The preliminary results of a search for TNOs using this new pipeline on data from the first HSC-SSP data release (Mar 2014 to Nov 2015) are also presented.Comment: 32 pages, 10 figures, 2 tables, submitted to HSC special issue in PAS

Discovery of A New Retrograde Trans-Neptunian Object: Hint of A Common Orbital Plane for Low Semi-Major Axis, High Inclination TNOs and Centaurs

Although the majority of Centaurs are thought to have originated in the scattered disk, with the high-inclination members coming from the Oort cloud, the origin of the high inclination component of trans-Neptunian objects (TNOs) remains uncertain. We report the discovery of a retrograde TNO, which we nickname "Niku", detected by the Pan-STARRS 1 Outer Solar System Survey. Our numerical integrations show that the orbital dynamics of Niku are very similar to that of 2008 KV$_{42}$ (Drac), with a half-life of $\sim 500$ Myr. Comparing similar high inclination TNOs and Centaurs ($q > 10$ AU, $a 60^\circ$), we find that these objects exhibit a surprising clustering of ascending node, and occupy a common orbital plane. This orbital configuration has high statistical significance: 3.8-$\sigma$. An unknown mechanism is required to explain the observed clustering. This discovery may provide a pathway to investigate a possible reservoir of high-inclination objects.Comment: 18 pages, 4 figures, 1 table, accepted for publication in ApJ Letter

Novel polythiophene derivatives functionalized withconjugated side-chain pendants comprisingtriphenylamine/carbazole moieties for photovoltaic cellapplications†

We synthesized a series of polythiophenes (PTs) featuring 2-ethylhexyl-substituted terthiophene (T) orquaterthiophene (BT) as the conjugated unit in the polymer backbone with pendant conjugated tertbutyl-substituted triphenylamine (tTPA)- or carbazole (tCz)-containing moieties as side chains, namelyPTtTPA, PBTtTPA, PTtCz and PBTtCz. Incorporating T and BT moieties into the polymer backbone andattaching tTPA or tCz units promoted efficient conjugation within the extended conjugated frameworksof the polymers, resulting in lower band-gap energies and red-shifting of the maximal UV-Visabsorption wavelength. The higher electron-donating ability of tTPA resulted in broader absorptionbands and lower band-gap energies of PTtTPA and PBTtTPA as compared with PTtCz and PBTtCz.Incorporation of the T and BT moieties into the polymer backbone enhanced the compatibility of PTand the fullerene derivative by reducing the side-chain density of PT, thus providing sufficient freevolume for efficient incorporation of [6,6]phenyl-C61-butyric acid methyl ester (PC61BM) into thepolymer chains. Polymer solar cells (PSCs) were fabricated by spin-coating a blend of each PT with thefullerene derivative (PC61BM) as a composite film-type photoactive layer; PBTtTPA/PC61BM-based PSCsshowed superior photovoltaic (PV) performance to PTtTPA/PC61BM-based PSCs in terms of conjugationand absorption band broadness. However, PBTtCz/PC61BM-based PSCs showed inferior PV performanceto PTtCz/PC61BM-based PSCs. The lower HOMO level led to a higher open-circuit voltage (Voc; 0.74 V)and larger photo-energy conversion efficiency (h; 2.77%) of PTtCz/PC61BM-based PSCs

Is real depreciation and expansionary fiscal policy effective? The case of Serbia

Applying the IS-MP-IA model to study the impacts of exchange rate movements, expansionary fiscal policy and other relevant variables in Serbia, we find that real appreciation of the dinar, a higher government deficit-to-GDP ratio, a lower real lending rate in the euro area, a lower lagged real oil price, a higher Germany’s real GDP and a lower expected inflation rate would promote economic growth

Impaired dendritic cell maturation and IL-10 production following H. pylori stimulation in gastric cancer patients

The current study was to investigate the interaction between Helicobacter pylori and human dendritic cells (DCs). Whether impaired DC function can influence the outcome of H. pylori infections. Human monocyte-derived DCs (MDDCs) from five gastric cancer patients and nine healthy controls were stimulated with H. pylori. Maturation markers of MDDC were examined by flow cytometry. IL-10 and TNF-α released by MDDCs and IL-17 produced by T cells were measured by ELISA. Regulatory signaling pathways of IL-10 were examined by ELISA, western blotting, and chromatin immunoprecipitation assay. The results showed that as compared with healthy individuals, the maturation marker CD40 in MDDCs, IL-17A expression from T cells, and IL-10 expression from MDDCs were significantly lower in gastric cancer patients. Blocking DC-SIGN, TLR2, and TLR4 could reverse H. pylori-associated IL-10 production. Activation of the p38 MAPK and NF-kB signaling pathways concomitant with decreased tri-methylated H3K9 and increased acetylated H3 accounted for the effect of H. pylori on IL-10 expression. Furthermore, upregulated IL-10 expression was significantly suppressed in H. pylori-pulsed MDDCs by histone acetyltransferase and methyltransferase inhibitors. Taken together, impaired DC function contributes to the less effective innate and adaptive immune responses against H. pylori seen in gastric cancer patients. H. pylori can regulate IL-10 production through Toll-like and DC-SIGN receptors, activates p-p38 MAPK signaling and the transcription factors NF-kB, and modulates histone modification

Be Stars in the Open Cluster NGC 6830

We report the discovery of 2 new Be stars, and re-identify one known Be star in the open cluster NGC 6830. Eleven H-alpha emitters were discovered using the H-alpha imaging photometry of the Palomar Transient Factory Survey. Stellar membership of the candidates was verified with photometric and kinematic information using 2MASS data and proper motions. The spectroscopic confirmation was carried out by using the Shane 3-m telescope at Lick observatory. Based on their spectral types, three H-alpha emitters were confirmed as Be stars with H-alpha equivalent widths > -10 Angstrom. Two objects were also observed by the new spectrograph SED-Machine on the Palomar 60 inch Telescope. The SED-Machine results show strong H-alpha emission lines, which are consistent with the results of the Lick observations. The high efficiency of the SED-Machine can provide rapid observations for Be stars in a comprehensive survey in the future.Comment: 11 pages, 8 figures, AJ in pres