150 research outputs found
A Flight Research Overview of WSPR, a Pilot Project for Sonic Boom Community Response
In support of NASAs ongoing effort to bring supersonic commercial travel to the public, NASA Dryden Flight Research Center and NASA Langley Research Center, in cooperation with other industry organizations, conducted a flight research experiment to identify the methods, tools, and best practices for a large-scale quiet (or low) sonic boom community human response test. The name of the effort was Waveforms and Sonic boom Perception and Response. Such tests will go towards building a dataset that governing agencies like the Federal Aviation Administration and International Civil Aviation Organization will use to establish regulations for acceptable sound levels of overland sonic booms. Until WSPR, there had never been an effort that studied the response of people in their own homes and performing daily activities to non-traditional, low sonic booms.WSPR was a NASA collaborative effort with several industry partners, in response to a NASA Aeronautics Research Mission Directorate Research Opportunities in Aeronautics. The primary contractor was Wyle. Other partners included Gulfstream Aerospace Corporation, Pennsylvania State University, Tetra Tech, and Fidell Associates, Inc.A major objective of the effort included exposing a community with the sonic boom magnitudes and occurrences expected in high-air traffic regions with a network of supersonic commercial aircraft in place. Low-level sonic booms designed to simulate those produced by the next generation of commercial supersonic aircraft were generated over a small residential community. The sonic boom footprint was recorded with an autonomous wireless microphone array that spanned the entire community. Human response data was collected using multiple survey methods. The research focused on essential elements of community response testing including subject recruitment, survey methods, instrumentation systems, flight planning and operations, and data analysis methods.This paper focuses on NASAs role in the efforts logistics and operations including human response subject recruitment, the operational processes involved in implementing the surveys throughout the community, instrumentation systems, logistics, flight planning, and flight operations. Findings discussed in this paper include critical lessons learned in all of those areas. The paper also discusses flight operations results. Analysis of the accuracy and repeatability of planning and executing the unique aircraft maneuver used to generate low sonic booms concluded that the sonic booms had overpressures within 0.15 pounds-per-square-feet of the planned values for 76 of t he attempts. Similarly, 90 of the attempts to generate low sonic booms within the community were successful
Probing Mechanical Properties of Graphene with Raman Spectroscopy
The use of Raman scattering techniques to study the mechanical properties of
graphene films is reviewed here. The determination of Gruneisen parameters of
suspended graphene sheets under uni- and bi-axial strain is discussed and the
values are compared to theoretical predictions. The effects of the
graphene-substrate interaction on strain and to the temperature evolution of
the graphene Raman spectra are discussed. Finally, the relation between
mechanical and thermal properties is presented along with the characterization
of thermal properties of graphene with Raman spectroscopy.Comment: To appear in the Journal of Materials Scienc
The Coiled Coils of Cohesin Are Conserved in Animals, but Not In Yeast
The SMC proteins are involved in DNA repair, chromosome condensation, and sister chromatid cohesion throughout Eukaryota. Long, anti-parallel coiled coils are a prominent feature of SMC proteins, and are thought to serve as spacer rods to provide an elongated structure and to separate domains. We reported recently that the coiled coils of mammalian condensin (SMC2/4) showed moderate sequence divergence (approximately 10-15%) consistent with their functioning as spacer rods. The coiled coils of mammalian cohesins (SMC1/3), however, were very highly constrained, with amino acid sequence divergence typically <0.5%. These coiled coils are among the most highly conserved mammalian proteins, suggesting that they make extensive contacts over their entire surface.Here, we broaden our initial analysis of condensin and cohesin to include additional vertebrate and invertebrate organisms and multiple species of yeast. We found that the coiled coils of SMC1/3 are highly constrained in Drosophila and other insects, and more generally across all animal species. However, in yeast they are no more constrained than the coils of SMC2/4 and Ndc80/Nuf2p, suggesting that they are serving primarily as spacer rods.SMC1/3 functions for sister chromatid cohesion in all species. Since its coiled coils apparently serve only as spacer rods in yeast, it is likely that this is sufficient for sister chromatid cohesion in all species. This suggests an additional function in animals that constrains the sequence of the coiled coils. Several recent studies have demonstrated that cohesin has a role in gene expression in post-mitotic neurons of Drosophila, and other animal cells. Some variants of human Cornelia de Lange Syndrome involve mutations in human SMC1/3. We suggest that the role of cohesin in gene expression may involve intimate contact of the coiled coils of SMC1/3, and impose the constraint on sequence divergence
RAD21 Cooperates with Pluripotency Transcription Factors in the Maintenance of Embryonic Stem Cell Identity
For self-renewal, embryonic stem cells (ESCs) require the expression of specific transcription factors accompanied by a particular chromosome organization to maintain a balance between pluripotency and the capacity for rapid differentiation. However, how transcriptional regulation is linked to chromosome organization in ESCs is not well understood. Here we show that the cohesin component RAD21 exhibits a functional role in maintaining ESC identity through association with the pluripotency transcriptional network. ChIP-seq analyses of RAD21 reveal an ESC specific cohesin binding pattern that is characterized by CTCF independent co-localization of cohesin with pluripotency related transcription factors Oct4, Nanog, Sox2, Esrrb and Klf4. Upon ESC differentiation, most of these binding sites disappear and instead new CTCF independent RAD21 binding sites emerge, which are enriched for binding sites of transcription factors implicated in early differentiation. Furthermore, knock-down of RAD21 causes expression changes that are similar to expression changes after Nanog depletion, demonstrating the functional relevance of the RAD21 - pluripotency transcriptional network association. Finally, we show that Nanog physically interacts with the cohesin or cohesin interacting proteins STAG1 and WAPL further substantiating this association. Based on these findings we propose that a dynamic placement of cohesin by pluripotency transcription factors contributes to a chromosome organization supporting the ESC expression program
Nuclear Import and Export Signals of Human Cohesins SA1/STAG1 and SA2/STAG2 Expressed in Saccharomyces cerevisiae
Abstract
Background: Human SA/STAG proteins, homologues of the yeast Irr1/Scc3 cohesin, are the least studied constituents of the
sister chromatid cohesion complex crucial for proper chromosome segregation. The two SA paralogues, SA1 and SA2, show
some specificity towards the chromosome region they stabilize, and SA2, but not SA1, has been shown to participate in
transcriptional regulation as well. The molecular basis of this functional divergence is unknown.
Methodology/Principal Findings: In silico analysis indicates numerous putative nuclear localization (NLS) and export (NES)
signals in the SA proteins, suggesting the possibility of their nucleocytoplasmic shuttling. We studied the functionality of
those putative signals by expressing fluorescently tagged SA1 and SA2 in the yeast Saccharomyces cerevisiae. Only the Nterminal
NLS turned out to be functional in SA1. In contrast, the SA2 protein has at least two functional NLS and also two
functional NES. Depending on the balance between these opposing signals, SA2 resides in the nucleus or is distributed
throughout the cell. Validation of the above conclusions in HeLa cells confirmed that the same N-terminal NLS of SA1 is
functional in those cells. In contrast, in SA2 the principal NLS functioning in HeLa cells is different from that identified in
yeast and is localized to the C-terminus.
Conclusions/Significance: This is the first demonstration of the possibility of non-nuclear localization of an SA protein. The
reported difference in the organization between the two SA homologues may also be relevant to their partially divergent
functions. The mechanisms determining subcellular localization of cohesins are only partially conserved between yeast and
human cells
Time perception and the experience of agency in meditation and hypnosis
Mindfulness meditation and hypnosis are related in opposing ways to awareness of intentions. The cold control theory of hypnosis proposes that hypnotic responding involves the experience of involuntariness while performing an actually intentional action. Hypnosis therefore relies upon inaccurate metacognition about intentional actions and experiences. Mindfulness meditation centrally involves awareness of intentions and is associated with improved metacognitive access to intentions. Therefore, mindfulness meditators and highly hypnotizable people may lie at opposite ends of a spectrum with regard to metacognitive access to intention‐related information. Here we review the theoretical background and evidence for differences in the metacognition of intentions in these groups, as revealed by chronometric measures of the awareness of voluntary action: the timing of an intention to move (Libet's “W” judgments) and the compressed perception of time between an intentional action and its outcome (“intentional binding”). We review these measures and critically evaluate their proposed connection to the experience of volition and sense of agency
Cohesin is required for higher-order chromatin conformation at the imprinted IGF2-H19 locus
Cohesin is a chromatin-associated protein complex that mediates sister chromatid cohesion by connecting replicated DNA molecules. Cohesin also has important roles in gene regulation, but the mechanistic basis of this function is poorly understood. In mammalian genomes, cohesin co-localizes with CCCTC binding factor (CTCF), a zinc finger protein implicated in multiple gene regulatory events. At the imprinted IGF2-H19 locus, CTCF plays an important role in organizing allele-specific higher-order chromatin conformation and functions as an enhancer blocking transcriptional insulator. Here we have used chromosome conformation capture (3C) assays and RNAi-mediated depletion of cohesin to address whether cohesin affects higher order chromatin conformation at the IGF2-H19 locus in human cells. Our data show that cohesin has a critical role in maintaining CTCF-mediated chromatin conformation at the locus and that disruption of this conformation coincides with changes in IGF2 expression. We show that the cohesin-dependent, higher-order chromatin conformation of the locus exists in both G1 and G2 phases of the cell cycle and is therefore independent of cohesin's function in sister chromatid cohesion. We propose that cohesin can mediate interactions between DNA molecules in cis to insulate genes through the formation of chromatin loops, analogous to the cohesin mediated interaction with sister chromatids in trans to establish cohesion
Specialized interfaces of Smc5/6 control hinge stability and DNA association
The Structural Maintenance of Chromosomes (SMC) complexes: cohesin, condensin and Smc5/6 are involved in the organization of higher-order chromosome structure—which is essential for accurate chromosome duplication and segregation. Each complex is scaffolded by a specific SMC protein dimer (heterodimer in eukaryotes) held together via their hinge domains. Here we show that the Smc5/6-hinge, like those of cohesin and condensin, also forms a toroidal structure but with distinctive subunit interfaces absent from the other SMC complexes; an unusual ‘molecular latch’ and a functional ‘hub’. Defined mutations in these interfaces cause severe phenotypic effects with sensitivity to DNA-damaging agents in fission yeast and reduced viability in human cells. We show that the Smc5/6-hinge complex binds preferentially to ssDNA and that this interaction is affected by both ‘latch’ and ‘hub’ mutations, suggesting a key role for these unique features in controlling DNA association by the Smc5/6 complex
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