The lncRNA HOTAIR transcription is controlled by HNF4α-induced chromatin topology modulation

The expression of the long noncoding RNA HOTAIR (HOX Transcript Antisense Intergenic RNA) is largely deregulated in epithelial cancers and positively correlates with poor prognosis and progression of hepatocellular carcinoma and gastrointestinal cancers. Furthermore, functional studies revealed a pivotal role for HOTAIR in the epithelial-to-mesenchymal transition, as this RNA is causal for the repressive activity of the master factor SNAIL on epithelial genes. Despite the proven oncogenic role of HOTAIR, its transcriptional regulation is still poorly understood. Here hepatocyte nuclear factor 4-α (HNF4α), as inducer of epithelial differentiation, was demonstrated to directly repress HOTAIR transcription in the mesenchymal-to epithelial transition. Mechanistically, HNF4α was found to cause the release of a chromatin loop on HOTAIR regulatory elements thus exerting an enhancer-blocking activity

The Origins of the Circumgalactic Medium in the FIRE Simulations

We use a particle tracking analysis to study the origins of the circumgalactic medium (CGM), separating it into (1) accretion from the intergalactic medium (IGM), (2) wind from the central galaxy, and (3) gas ejected from other galaxies. Our sample consists of 21 FIRE-2 simulations, spanning the halo mass range log(Mh/Msun) ~ 10-12 , and we focus on z=0.25 and z=2. Owing to strong stellar feedback, only ~L* halos retain a baryon mass >~50% of their cosmic budget. Metals are more efficiently retained by halos, with a retention fraction >~50%. Across all masses and redshifts analyzed >~60% of the CGM mass originates as IGM accretion (some of which is associated with infalling halos). Overall, the second most important contribution is wind from the central galaxy, though gas ejected or stripped from satellites can contribute a comparable mass in ~L* halos. Gas can persist in the CGM for billions of years, resulting in well-mixed halo gas. Sight lines through the CGM are therefore likely to intersect gas of multiple origins. For low-redshift ~L* halos, cool gas (T<10^4.7 K) is distributed on average preferentially along the galaxy plane, however with strong halo-to-halo variability. The metallicity of IGM accretion is systematically lower than the metallicity of winds (typically by >~1 dex), although CGM and IGM metallicities depend significantly on the treatment of subgrid metal diffusion. Our results highlight the multiple physical mechanisms that contribute to the CGM and will inform observational efforts to develop a cohesive picture.Comment: 23 pages, 22 figures. Minor revisions from previous version. Online interactive visualizations available at zhafen.github.io/CGM-origins and zhafen.github.io/CGM-origins-pathline

Failure Analysis of Flow-induced Vibration Problem of in-serviced Duplex Stainless Steel Piping System in Oil and Gas Industry

Failure of the duplex stainless steel piping system in oil and gas industry can have disastrous effects. In this study, a novel method of failure analysis of flow-induced vibration problem of in-serviced duplex stainless steel piping system is proposed. The proposed non-destructive technique is able to determine a suitable operating condition for continuous operation without failure. The technique relies on the combined operation of operational modal analysis, operating deflection shape analysis and linear elastic finite element analysis. The effect of different operating conditions for two distinct valve opening cases (i.e. fully opened and partially opened) on the dynamic stress is examined, and they are utilised for forecasting purpose in failure analysis. The result shows that maximum operating conditions are 360 and 400 mmscfd for fully opened and partially opened flow control valves, respectively. Beyond this limit, the piping system most likely will fail

Internal structure of virtual communications in communities of inquiry in higher education: Phases, evolution and participants’ satisfaction

This study investigates the phases of development of synchronous and asynchronous virtual communication produced in a community of inquiry (CoI) by analyzing the internal structure of each intervention in the forum and each chat session to determine the evolution of their social, cognitive and teaching character. It also analyzes the participating higher education students’ satisfaction with the activities, with the professors’ actions, and with themselves. We use a mixed methodology that includes content analysis of the virtual communications by crossing two categorization systems: (1) type of communication according to the model adopted from Garrison, Anderson and Archer (social, cognitive and teaching presence) and (2) phases in the evolution of the communication (initiation, proposal, development, opinion/closing and good-byes). The data are relevant to the students’ satisfaction and grades earned. The results suggest differences in the quantity and content of the communication in each phase and an evolution from social to cognitive elements, ending with social contributions. The students are satisfied with the virtual communications related to both the activities and the professors and evaluate themselves positively

Influence of uncorrelated overlayers on the magnetism in thin itinerant-electron films

The influence of uncorrelated (nonmagnetic) overlayers on the magnetic properties of thin itinerant-electron films is investigated within the single-band Hubbard model. The Coulomb correlation between the electrons in the ferromagnetic layers is treated by using the spectral density approach (SDA). It is found that the presence of nonmagnetic layers has a strong effect on the magnetic properties of thin films. The Curie temperatures of very thin films are modified by the uncorrelated overlayers. The quasiparticle density of states is used to analyze the results. In addition, the coupling between the ferromagnetic layers and the nonmagnetic layers is discussed in detail. The coupling depends on the band occupation of the nonmagnetic layers, while it is almost independent of the number of the nonmagnetic layers. The induced polarization in the nonmagnetic layers shows a long-range decreasing oscillatory behavior and it depends on the coupling between ferromagnetic and nonmagnetic layers.Comment: 9 pages, RevTex, 6 figures, for related work see: http://orion.physik.hu-berlin.d

Setting The Pace: Examining Cognitive Processing in MOOC Discussion Forums With Automatic Text Analysis

Learning analytics focuses on extracting meaning from large amounts of data. One of the largest datasets in education comes from Massive Open Online Courses (MOOCs) that typically feature enrollments in the tens of thousands. Analyzing MOOC discussion forums presents logistical issues, resulting chiefly from the size of the dataset, which can create challenges for understanding and adequately describing student behaviors. Utilizing automatic text analysis, this study built a hierarchical linear model that examines the influence of the pacing condition of a massive open online course (MOOC), whether it is self-paced or instructor-paced, on the demonstration of cognitive processing in a HarvardX MOOC. The analysis of 2,423 discussion posts generated by 671 students revealed the number of dictionary words used were positively associated with cognitive processing while analytical thinking and clout was negatively associated. We found that none of the student background information (gender, education), status of the course engagement (explored or completed), or the course pace (self-paced versus instructor paced) significantly influenced the cognitive processing of the postings

Comparative analysis of an experimental subcellular protein localization assay and in silico prediction methods

The subcellular localization of a protein can provide important information about its function within the cell. As eukaryotic cells and particularly mammalian cells are characterized by a high degree of compartmentalization, most protein activities can be assigned to particular cellular compartments. The categorization of proteins by their subcellular localization is therefore one of the essential goals of the functional annotation of the human genome. We previously performed a subcellular localization screen of 52 proteins encoded on human chromosome 21. In the current study, we compared the experimental localization data to the in silico results generated by nine leading software packages with different prediction resolutions. The comparison revealed striking differences between the programs in the accuracy of their subcellular protein localization predictions. Our results strongly suggest that the recently developed predictors utilizing multiple prediction methods tend to provide significantly better performance over purely sequence-based or homology-based predictions

Should Research Ethics Encourage the Production of Cost-Effective Interventions?

This project considers whether and how research ethics can contribute to the provision of cost-effective medical interventions. Clinical research ethics represents an underexplored context for the promotion of cost-effectiveness. In particular, although scholars have recently argued that research on less-expensive, less-effective interventions can be ethical, there has been little or no discussion of whether ethical considerations justify curtailing research on more expensive, more effective interventions. Yet considering cost-effectiveness at the research stage can help ensure that scarce resources such as tissue samples or limited subject popula- tions are employed where they do the most good; can support parallel efforts by providers and insurers to promote cost-effectiveness; and can ensure that research has social value and benefits subjects. I discuss and rebut potential objections to the consideration of cost-effectiveness in research, including the difficulty of predicting effectiveness and cost at the research stage, concerns about limitations in cost-effectiveness analysis, and worries about overly limiting researchers’ freedom. I then consider the advantages and disadvantages of having certain participants in the research enterprise, including IRBs, advisory committees, sponsors, investigators, and subjects, consider cost-effectiveness. The project concludes by qualifiedly endorsing the consideration of cost-effectiveness at the research stage. While incorporating cost-effectiveness considerations into the ethical evaluation of human subjects research will not on its own ensure that the health care system realizes cost-effectiveness goals, doing so nonetheless represents an important part of a broader effort to control rising medical costs