Q-Mer Analysis: A Generalized Method for Analyzing RNA-Seq Data

Background: RNA-Seq data are usually summarized by counting the number of transcript reads aligned to each gene. However, count-based methods do not take alignment information, where and how each read was mapped in the gene, into account. This information is essential to characterize samples accurately. In this study, we developed a method to summarize RNA-Seq data without losing alignment information. Results: To include alignment information, we introduce “q-mer analysis,” which summarizes RNA-Seq data with 4q kinds of q-length oligomers. Using publicly available RNA-Seq datasets, we demonstrate that at least q ≧ 9 is required for capturing alignment information in Homo sapiens. It should be noted that 49 = 262,144 is approximately 10 times larger than the number of genes in H. sapiens (20,022 genes). Furthermore, principal component analysis showed that q-mer analysis with q = 14 linearly distinguished samples from controls, while a count-based method failed. These results indicate that alignment information is essential to characterize transcriptomics samples. Conclusions: In conclusion, we introduce q-mer analysis to include alignment information in RNA-Seq analysis and demonstrate the superiority of q-mer analysis over count-based methods in that q-mer analysis can distinguish case samples from controls. Combining RNA-Seq research with q-mer analysis could be useful for identifying distinguishing transcriptomic features that could provide hypotheses for disease mechanisms.

On Loving God Contrary to a Divine Command

Among the most widely discussed of William Ockham’s texts on ethics is his Quodlibet III, q. 14. But despite a large literature on this question, there is no consensus on what Ockham’s answer is to the central question raised in it, specifically, what obligations one would have if one were to receive a divine command to not love God. (Surprisingly, there is also little explicit recognition in the literature of this lack of consensus.) Via a close reading of the text, the author argues, contrary to much of the literature, that Ockham believes that if one were given this command, one would be obligated to refrain from loving God and would also be able to fulfill this obligation without any moral wrongdoing. Among other results, this study will help clarify Ockham’s much-discussed claim that loving God is “a necessarily virtuous act.”

Chinese medicine (Q-14) in the Treatment of Patients with Coronavirus Disease 2019 (COVID-19): A Single-center, Open label, Randomised Controlled Trial

ABSTRACTOBJECTIVETo evaluate the efficacy and safety of Chinese medicine (Q-14) plus standard care compared with standard care alone in adult with coronavirus disease 2019 (COVID-19).Study DESIGNSingle-center, open label, randomised controlled trial.SETTINGWuhan Jinyintan Hospital, Wuhan, China, February 27 to March 27, 2020.PARTICIPANTS204 patients with laboratory confirmed COVID-19 were randomised in to treatment group and control group, which was 102 patients each group.INTERVENTIONSIn treatment group, Q-14 was administrated at 10g (granules), twice daily for 14 days and plus standard care. In control group, patients were given standard care alone for 14 days.MAIN OUTCOME MEASUREThe primary outcome was conversion time of SARS-CoV-2 viral assay. Adverse events were analyzed in the safety population.RESULTSAmong 204 patients, 195 were analyzed according to the intention to treat principle. There were 149 patients (71 vs. 78 in treatment group and control group respectively) turning to negative via SARS-CoV-2 viral assay. No statistically significance showed in conversion time between treatment group and control group (FAS: Median (IQR): 10.00 (9.00-11.00) vs. 10.00 (9.00-11.00); Mean rank: 67.92 vs. 81.44; P=0.051.). Time to recovery of fever was shorter in treatment group as compared in control group. The disappearance rate of symptom in cough, fatigue, chest discomfort was significantly higher in treatment group. In chest computed tomography (Chest CT) examinations, overall evaluation of chest CT examination after treatment compared with baseline showed more patients improved in treatment group .There were no significant differences in the other outcomes.CONCLUSIONAdministration of Q-14 on standard care for COVID-19 was useful for improvement of symptoms (such as fever, cough, fatigue and chest discomfort), while did not result in a significantly higher probability of negative conversion of SARS-CoV-2 viral assay. No serious adverse events were reported.TRIAL REGISTRATIONChiCTR2000030288

Wzorniki Normanda i Quaglia. Wykorzystanie publikacji francuskich przy realizacji nagrobków na cmentarzach Warszawy w latach 1840-1860

Rozpowszechnioną w XIX w. praktyką było wykorzystywanie wzorników przy realiza­cji pomników grobowych na cmentarzach europejskich. Cmentarze warszawskie nie są tu wyjątkiem. Najstarsze zachowane nagrobki pochodzą z przełomu XVIII i XIX w. Liczniejszą grupę stanowią dopiero obiekty powstałe w latach 30. i 40. XIX w. na cmentarzu powązkowskim oraz dwóch ewangelickich: luterańskim i kalwińskim. Są to pomniki utrzymane albo w stylistyce neogotyckiej, albo klasycystyczno-empirowej z wyraźnymi odniesieniami do sztuki greckiej, rzymskiej lub egipskiej. Ostatnia wymieniona grupa inspirowana była w dużej mierze wzornikami francuskimi. Opracowania Louisa Marie Normanda i Ferdinanda Quaglia z 1832 r. oraz dzieło Josepha Marty z 1839 r. stały się źródłem wielu naśladownictw. Tematem pierwszej części artykułu są przykłady zaczerpnięte z wydań Normanda i Quaglia. Spośród pomników zostały szerzej omówione: mauzoleum Petyskusów na cmentarzu ewangelicko-augsburskim (al. 11, nr 25) oraz nagrobki – rodziny Sokołowskich na Powązkach (kw. 14, rz. 6), Karola Fryderyka Woyde na cmentarzu ewangelicko-reformowanym (kw. K, rz. 2), Michała Włodka (kw. 14, rz. 5) i Ignacego Zielińskiego (kw. 33, rz. 3) na Powązkach, Teodora Tripplina na cmentarzu ewangelicko-reformowanym (kw. S, rz. 1) oraz rodzinny Brandtów na cmentarzu rzymskokatolickim w Radomiu (kw. 5a). Druga część artykułu poświęcona będzie omówieniu przykładów pochodzących z wzor­nika Josepha Marty. Tam też dopiero zostaną zamieszczone wnioski końcowe. The use of French templates during the execution of tombstones for the cemeteries of Warsaw from 1840 to 1860. Normand and Quaglia templates In the XIXth century it was a common practice to use templates while executing tombstones for European cemeteries. The cemeteries of Warsaw are no exception to the policy. The eldest preserved tombstones date back up to the turn of the 18th and the 19th centuries. A more numerous group consists of objects constructed no earlier than in the 30’s and the 40’s, at Powązki Cemetry as well as at two Evangelical Cemeteries: Lutheran and Calvin. They are tombstones either sticking to Neo-gothic style or to Classicist- Empire with visible influence of Greek, Roman and Egyptian art. The latter was, in its vast majority, inspired by French templates. Studies by Louis Marie Normand and Ferdinando Quaglia from 1832 as well as the masterpiece by Joseph Marty from 1839 have been sources of several emulations. In the first part of the article examples from Normand and Quaglia editions were given. Among other tombstones mentioned the following were given a more meticulous analysis: The Petyskus Mausoleum at Evangelical-Augsburg Cemetery (Ave. 11, n° 25) as well as the following tombstones: of the Sokołowscy at Powązki Cemetery (q. 14, r. 6), of Karol Fryderyk Woyda at Evangelical-Reformed Cemetery (q. K, r. 2), of Michał Włodek (q. 14, r 5) and of Ignacy Zieliński (q. 33, r. 3) at Powązki Cemetery, the one of Teodor Tripplin at Evangelical-Reformed Cemetery (q. S, r. 1) as well as The Brandt family at Roman Catholic Cemetery in Radom (q. 5a). In the second part of the article examples from Joseph Mary templates are analyzed. It is also were key findings and conclusions are specified.

Identification of New Peptides from Fermented Milk Showing Antioxidant Properties: Mechanism of Action

Due to their beneficial properties, fermented foods are considered important constituents of the human diet. They also contain bioactive peptides, health-promoting compounds studied for a wide range of effects. In this work, several antioxidant peptides extracted from fermented milk proteins were investigated. First, enriched peptide fractions were purified and analysed for their antioxidant capacity in vitro and in a cellular model. Subsequently, from the most active fractions, 23 peptides were identified by mass spectrometry MS/MS), synthesized and tested. Peptides N-15-M, E-11-F, Q-14-R and A-17-E were selected for their antioxidant effects on Caco-2 cells both in the protection against oxidative stress and inhibition of ROS production. To define their action mechanism, the activation of the Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2(Keap1/Nrf2) pathway was studied evaluating the translocation of Nrf2 from cytosol to nucleus. In cells treated with N-15-M, Q-14-R and A-17-E, a higher amount of Nrf2 was found in the nucleus with respect to the control. In addition, the three active peptides, through the activation of Keap1/Nrf2 pathway, led to overexpression and increased activity of antioxidant enzymes. Molecular docking analysis confirmed the potential ability of N-15-M, Q-14-R and A-17-E to bind Keap1, showing their destabilizing effect on Keap1/Nrf2 interaction.