Detection of suspicious interactions of spiking covariates in methylation data

BACKGROUND: In methylation analyses like epigenome-wide association studies, a high amount of biomarkers is tested for an association between the measured continuous outcome and different covariates. In the case of a continuous covariate like smoking pack years (SPY), a measure of lifetime exposure to tobacco toxins, a spike at zero can occur. Hence, all non-smokers are generating a peak at zero, while the smoking patients are distributed over the other SPY values. Additionally, the spike might also occur on the right side of the covariate distribution, if a category "heavy smoker" is designed. Here, we will focus on methylation data with a spike at the left or the right of the distribution of a continuous covariate. After the methylation data is generated, analysis is usually performed by preprocessing, quality control, and determination of differentially methylated sites, often performed in pipeline fashion. Hence, the data is processed in a string of methods, which are available in one software package. The pipelines can distinguish between categorical covariates, i.e. for group comparisons or continuous covariates, i.e. for linear regression. The differential methylation analysis is often done internally by a linear regression without checking its inherent assumptions. A spike in the continuous covariate is ignored and can cause biased results. RESULTS: We have reanalysed five data sets, four freely available from ArrayExpress, including methylation data and smoking habits reported by smoking pack years. Therefore, we generated an algorithm to check for the occurrences of suspicious interactions between the values associated with the spike position and the non-spike positions of the covariate. Our algorithm helps to decide if a suspicious interaction can be found and further investigations should be carried out. This is mostly important, because the information on the differentially methylated sites will be used for post-hoc analyses like pathway analyses. CONCLUSIONS: We help to check for the validation of the linear regression assumptions in a methylation analysis pipeline. These assumptions should also be considered for machine learning approaches. In addition, we are able to detect outliers in the continuous covariate. Therefore, more statistical robust results should be produced in methylation analysis using our algorithm as a preprocessing step

Nova Aquilae 1918 (V603 Aql) Faded by 0.44 mag/century from 1938-2013

We present the light curve of the old nova V603 Aql (Nova Aql 1918) from 1898-1918 and 1934-2013 using 22,721 archival magnitudes. All of our magnitudes are either in, or accurately transformed into, the Johnson $B$ and $V$ magnitude systems. This is vital because offsets in old sequences and the visual-to-$V$ transformation make for errors from 0.1-1.0 magnitude if not corrected. Our V603 Aql light curve is the first time that this has been done for any nova. Our goal was to see the evolution of the mass accretion rate on the century time scale, and to test the long-standing prediction of the Hibernation model that old novae should be fading significantly in the century after their eruption is long over. The 1918 nova eruption was completely finished by 1938 when the nova decline stopped, and when the star had faded to fainter than its pre-nova brightness of $B=11.43 \pm 0.03$ mag. We find that the nova light from 1938-2013 was significantly fading, with this being seen consistently in three independent data sets (the Sonneberg plates in $B$, the AAVSO $V$ light curve, and the non-AAVSO $V$ light curve). We find that V603 Aql is declining in brightness at an average rate of $0.44 \pm 0.04$ mag per century since 1938. This work provides remarkable confirmation of an important prediction of the Hibernation model.Comment: 13 pages, 1 figure, 2 electronic online data tables, Accepted for publication ApJLet

Discovery of the 2010 Eruption and the Pre-Eruption Light Curve for Recurrent Nova U Scorpii

We report the discovery by B. G. Harris and S. Dvorak on JD 2455224.9385 (2010 Jan 28.4385 UT) of the predicted eruption of the recurrent nova U Scorpii (U Sco). We also report on 815 magnitudes (and 16 useful limits) on the pre-eruption light curve in the UBVRI and Sloan r' and i' bands from 2000.4 up to 9 hours before the peak of the January 2010 eruption. We found no significant long-term variations, though we did find frequent fast variations (flickering) with amplitudes up to 0.4 mag. We show that U Sco did not have any rises or dips with amplitude greater than 0.2 mag on timescales from one day to one year before the eruption. We find that the peak of this eruption occurred at JD 2455224.69+-0.07 and the start of the rise was at JD 2455224.32+-0.12. From our analysis of the average B-band flux between eruptions, we find that the total mass accreted between eruptions is consistent with being a constant, in agreement with a strong prediction of nova trigger theory. The date of the next eruption can be anticipated with an accuracy of +-5 months by following the average B-band magnitudes for the next ~10 years, although at this time we can only predict that the next eruption will be in the year 2020+-2.Comment: Astronomical Journal submitted, 36 pages, 3 figures, full table

pH- and Temperature-Dependent Kinetics of the Oxidation Reactions of OH with Succinic and Pimelic Acid in Aqueous Solution

Rate constants for the aqueous-phase reactions of the hydroxyl radical with the dicarboxylic acids, succinic acid and pimelic acid were determined using the relative rate technique over the temperature range 287 K ≤ T ≤ 318 K and at pH = 2.0, 4.6 or 4.9 and 8.0. OH radicals were generated by H2O2 laser flash photolysis while thiocyanate was used as a competitor. The pH values were adjusted to obtain the different speciation of the dicarboxylic acids. The following Arrhenius expressions were determined (in units of L mol-1 s-1): succinic acid, k(T, AH2) (2.1 x 0.1) ± 1010 exp[(-1530 x 250 K)/T], k(T, AH-) (1.8 x 0.1) ± 1010 exp[(-1070 x 370 K)/T], k(T, A2-) (2.9 x 0.2) ± 1011 exp[(-1830 x 350 K)/T] and pimelic acid, k(T, AH2) (7.3 x 0.2) ± 1010 exp[(-1040 x 140 K)/T], k(T, AH-) (1.8 x 0.1) ± 1011 exp[(-1200 x 240 K)/T], k(T, A2-) (1.4 x 0.1) ± 1012 exp[(-1830 x 110 K)/T]. A general OH radical reactivity trend for dicarboxylic acids was found as k(AH2) < k(AH-) < k(A2-). By using the pH and temperature dependent rate constants, source and sinking processes in the tropospheric aqueous phase can be described precisely. © 2020 by the authors

In vitro induction of Entamoeba gingivalis cyst-like structures from trophozoites in response to antibiotic treatment

Background: Entamoeba gingivalis (E. gingivalis) is an anaerobic protozoan that is strongly associated with inflamed periodontal pockets. It is able to invade the mucosal epithelium of the human host, where it can feed on epithelial cells and elicit a severe innate immune response. Unlike other Entamoeba species, it is considered that E. gingivalis cannot form cysts, because it is a non-infectious protozoan. The lack of encystation capability would make it susceptible to periodontal treatment. However, it is not clear how the human host becomes infected with E. gingivalis trophozoites. We investigated the ability of E. gingivalis to encapsulate in response to an unfavorable environment in vitro. Methods: Different strains of E. gingivalis, isolated from inflamed periodontal pocket samples, were cultured for 8 days in the presence or absence of the antimicrobials amoxycillin and metronidazole. To reveal cyst formation, we investigated the morphology and ultrastructure of the amoeba by light, fluorescence, transmission and scanning electron microscopy. We also used the fluorescent dye calcofluor white M2R to demonstrate chitin present in the cyst wall. Results: We observed exocysts and an intra-cystic space separating the encapsulated trophozoite from the environment. Remarkably, cysts showed a smooth surface, polygonal edges and smaller size compared to free-living trophozoites. In addition, encapsulated trophozoites that detached from the cyst wall had a dense cytoplasma without phagocytic vesicles. The cyst walls consisted of chitin as in other Entamoba species. The encapsulated trophozoids were mononuclear after antibioticinduced encapsulation. Discussion: We conclude that E. gingivalis cyst formation has significant implications for dissemination and infection and may explain why established treatment approaches often fail to halt periodontal tissue destruction during periodontitis and peri-implantitis