Gene set enrichment tests (a.k.a. functional enrichment analysis) are among the most frequently used methods in computational biology. Despite this popularity, there are concerns that these methods ...are being applied incorrectly and the results of some peer-reviewed publications are unreliable. These problems include the use of inappropriate background gene lists, lack of false discovery rate correction and lack of methodological detail. To ascertain the frequency of these issues in the literature, we performed a screen of 186 open-access research articles describing functional enrichment results. We find that 95% of analyses using over-representation tests did not implement an appropriate background gene list or did not describe this in the methods. Failure to perform p-value correction for multiple tests was identified in 43% of analyses. Many studies lacked detail in the methods section about the tools and gene sets used. An extension of this survey showed that these problems are not associated with journal or article level bibliometrics. Using seven independent RNA-seq datasets, we show misuse of enrichment tools alters results substantially. In conclusion, most published functional enrichment studies suffered from one or more major flaws, highlighting the need for stronger standards for enrichment analysis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
The donor–acceptor (D-A) type of conjugated polymers has emerged as the paradigm of the third generation of electronically conducting polymers demonstrating improved infrared activity and ...intrinsic electronic conductivity. Judicious selection of donor (D) and acceptor (A) monomers for copolymerization can further fine-tune these properties. Notably, for such refinement, natural compounds provide many conjugated molecules with various functional groups. Berberine cation (Ber
+
) found in
Coscinium fenestratum
has extensive conjugation and contains both an electron deficient isoquinolium A moiety and electron-rich D-type methylenedioxy and methoxy groups. The incorporation of natural products in electronic materials is a novel area of research which opens a wide scope for future electronic and optoelectronic devices. Investigation of their fundamental properties via computer simulations is therefore important. In this study, quantum chemical calculations are performed using density functional theory (DFT) to investigate the electronic and optical properties of oligomers of Ber
+
and 3,4-ethylenedioxythiophene (EDOT) and to explore the possibilities for homo-polymerization of Ber
+
and its copolymerization with EDOT. It has been revealed that homo-polymerization is not favoured but copolymerization with EDOT is possible. As such, Ber
+
was copolymerized with EDOT and the copolymers formed by electro-polymerization are extensively characterised and the D-A behaviour of the copolymers verified. Furthermore, the theoretical predictions have been compared with the experimental data.
Achieving low carbon buildings is seen as a key concept in order to reduce carbon emission and mitigate climate change. In contrast to operational emission, material related embodied carbon (EC) in ...the built environment plays a pivotal role, with the continuous consumption of high carbon emitting materials. This research relates to the ‘Cradle-to-Gate’ system boundary, while limiting its focus on building design stage decisions. A hybrid analysis approach was adopted - a bottom-up process with steps encompassing mass analysis, EC calculation, highlighting carbon hotspots, and ultimately the identification of critical building components. As a case study, multi-storey housing was selected as a critical building typology, in Sri Lanka. The results reveal ‘walls’ as a carbon hotspot that needs to be explored in strategies for mitigation. Substantial EC savings were seen in the selection of fly ash blocks as an alternate material to clay brick or cement block. Changes to the configuration of walls, specifically, bonding patterns and non-inclusion of a plaster layer, also showed savings. This paper, contributes to the understanding of material selection implications - in the cradle-to-gate stage - for the reduction of carbon emissions in mid-rise housing, in the context of Sri Lanka.
Replication Protein A (RPA), the major eukaryotic single stranded DNA-binding protein, binds to exposed ssDNA to protect it from nucleases, participates in a myriad of nucleic acid transactions and ...coordinates the recruitment of other important players. RPA is a heterotrimer and coats long stretches of single-stranded DNA (ssDNA). The precise molecular architecture of the RPA subunits and its DNA binding domains (DBDs) during assembly is poorly understood. Using cryo electron microscopy we obtained a 3D reconstruction of the RPA trimerisation core bound with ssDNA (∼55 kDa) at ∼4.7 Å resolution and a dimeric RPA assembly on ssDNA. FRET-based solution studies reveal dynamic rearrangements of DBDs during coordinated RPA binding and this activity is regulated by phosphorylation at S178 in RPA70. We present a structural model on how dynamic DBDs promote the cooperative assembly of multiple RPAs on long ssDNA.
The plume of Enceladus is thought to originate from the dispersion of a liquid source beneath the icy crust. Cryovolcanic activity on Enceladus may present a direct way of accessing material ...originating from the potentially habitable subsurface ocean. One way to test the hypothesis of whether life is present within the ocean of Enceladus would be to investigate the plume material for the presence of microbial life. In this study, we investigated the entrainment of
within Enceladus-like fluids under boiling conditions caused by exposure of the fluids to low pressure. We show that boiling, associated with exposure of a fluid to low pressure, works as a mechanism for dispersing bacteria in Enceladus plume-like environments. Exposure of Enceladus-type fluids (0.01-0.1 molal Na
CO
and 0.05-0.2 molal NaCl) to low pressure (5 mbar) results in the dispersion of bacteria in droplets that evaporate to produce particles of salt. We find that, for particles with radius (
) ≤ 10 μm, the number of dispersed particles containing cells was between 7.7% and 10.9%. However, for larger particles 10 <
≤ 50 μm, 64.4% and 56.4% contained cells for lower and upper end-member solutions, respectively. Our results suggest that the gravity-induced size sorting of plume particles will result in plume deposits closer to the vent source containing a larger volume of biological material than within the plume. If life is present in the ocean of Enceladus, we would expect that it would be effectively entrained and deposited on the surface; therefore, it would be accessible with a surface-lander-based instrument.
This paper focuses on a fuzzy logic based intelligent decision making system that aims to improve the safety of marine vessels by avoiding collision situations. It can be implemented in a decision ...support system of an oceangoing vessel or included in the process of autonomous ocean navigation. Although Autonomous Guidance and Navigation (AGN) is meant to be an important part of future ocean navigation due to the associated cost reduction and improved maritime safety, intelligent decision making capabilities should be an integrated part of the future AGN system in order to improve autonomous ocean navigational facilities. In this study, the collision avoidance of the Target vessel with respect to the vessel domain of the Own vessel has been analyzed and input, and output fuzzy membership functions have been derived. The if-then rule based decision making process and the integrated novel fuzzy inference system are formulated and implemented on the MATLAB software platform. Simulation results are presented regarding several critical collision conditions where the Target vessel fails to take appropriate actions, as the “Give way” vessel to avoid collision situations. In these situations, the Own vessel is able to take critical actions to avoid collisions, even when being the “Stand on” vessel. Furthermore, all decision rules are formulated in accordance with the International Maritime Organization Convention on the International Regulations for Preventing Collisions at Sea (COLREGs), 1972, to avoid conflicts that might occur during ocean navigation.
This paper focuses on the formulation of a decision-action execution model that can facilitate intelligent collision avoidance features in ocean navigation systems, while respecting the Convention on ...the International Regulations for Preventing Collisions at Sea (COLREGs) rules and regulations of collision avoidance. The decision/action process in this work consists of a fuzzy-logic-based parallel decision-making (PDM) module whose decisions are formulated into sequential actions by a Bayesian-network-based module. Therefore, the paper presents a collision avoidance system (CAS) that is capable of making multiple parallel collision avoidance decisions regarding several target vessel collision conditions, and those decisions are executed as sequential actions to avoid complex collision situations in ocean navigation.
During the 1960s, Edgar Dale published the concept that learners are likely to retain more information if they see and hear information rather than just listen. Therefore, many educational ...applications have been created for students to learn theoretical concepts through visuals and in an interactive manner. Microsoft (MS) Excel has been used in many of these applications due to ease of use and widespread applicability. The main objective of this research is to introduce an MS Excel application to study the theoretical concepts associated with acid–base titrations. This application allows the user to select the type of titration, K a/K b values where applicable, concentrations of the reagents, titration volume, commonly used indicators, and follow the variation in the titration curve. With the use of the application, students can clearly visualize the change in pH during the titration, buffer region, and the effect of reagent concentrations and K a/K b values on the titration curves. It further allows the user to determine the end point of the titration via a first derivative plot, observe the variation in fractional composition of the reactive species with pH, and identify the indicator best suited for the titration. The application was proven successful when used to teach the concepts of acid–base titrations to a group of high school students.
Phorbol 12-myristate 13-acetate (PMA) promotes skin cancer in rodents. The mutations found in murine tumors are similar to those found in human skin cancers, and PMA promotes proliferation of human ...skin cells. PMA treatment of human keratinocytes increases the synthesis of APOBEC3A, an enzyme that converts cytosines in single-stranded DNA to uracil, and mutations in a variety of human cancers are attributed to APOBEC3A or APOBEC3B expression. We tested here the possibility that induction of APOBEC3A by PMA causes genomic accumulation of uracils that may lead to such mutations. When a human keratinocyte cell line was treated with PMA, both APOBEC3A and APOBEC3B gene expression increased, anti-APOBEC3A/APOBEC3B antibody bound a protein(s) in the nucleus, and nuclear extracts displayed cytosine deamination activity. Surprisingly, there was little increase in genomic uracils in PMA-treated wild-type or uracil repair-defective cells. In contrast, cells transfected with a plasmid expressing APOBEC3A acquired more genomic uracils. Unexpectedly, PMA treatment, but not APOBEC3A plasmid transfection, caused a cessation in cell growth. Hence, a reduction in single-stranded DNA at replication forks may explain the inability of PMA-induced APOBEC3A/APOBEC3B to increase genomic uracils. These results suggest that the proinflammatory PMA is unlikely to promote extensive APOBEC3A/APOBEC3B-mediated cytosine deaminations in human keratinocytes.
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