1,159 research outputs found
The triggering of MHD instabilities through photospheric footpoint motions
The results of 3D numerical simulations modelling the twisting of a coronal loop due to photospheric vortex motions are presented. The simulations are carried out using an initial purely axial field and an initial equilibrium configuration with twist, . The non-linear and resistive evolutions of the instability are followed. The magnetic field is twisted by the boundary motions into a loop which initially has boundary layers near the photospheric boundaries as has been suggested by previous work. The boundary motions increase the twist in the loop until it becomes unstable. For both cases the boundary twisting triggers the kink instability. In both cases a helical current structure wraps itself around the kinked central current. This current scales linearly with grid resolution indicating current sheet formation. For the cases studied 35-40% of the free magnetic energy is released. This is sufficient to explain the energy released in a compact loop flare
An assessment of high touch object cleaning thoroughness using a fluorescent marker in two Australian hospitals
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Mimicking the Impact of Infant Tongue Peristalsis on Behavior of Solid Oral Dosage Forms Administered During Breastfeeding.
An in vitro simulation system was developed to study the effect of an infant's peristaltic tongue motion during breastfeeding on oral rapidly disintegrating tablets in the mouth, for use in rapid product candidate screening. These tablets are being designed for use inside a modified nipple shield worn by a mother during breastfeeding, a proposed novel platform technology to administer drugs and nutrients to breastfeeding infants. In this study, the release of a model compound, sulforhodamine B, from tablet formulations was studied under physiologically relevant forces induced by compression and rotation of a tongue mimic. The release profiles of the sulforhodamine B in flowing deionized water were found to be statistically different using 2-way ANOVA with matching, when tongue mimic rotation was introduced for 2 compression levels representing 2 tongue strengths (p = 0.0013 and p < 0.0001 for the lower and higher compression settings, respectively). Compression level was found to be a significant factor for increasing model compound release at rotational rates representing nonnutritive breastfeeding (p = 0.0162). This novel apparatus is the first to simulate the motion and pressures applied by the tongue and could be used in future infant oral product development.This work was made possible through the generous support of the Saving Lives at Birth partners: the United States Agency for International Development (USAID), the Government of Norway, the Bill & Melinda Gates Foundation (grant number: OPP1129832), Grand Challenges Canada, and the UK Department for International Development (DFID); as well as the Gates Cambridge Trust.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.xphs.2016.08.00
Characterising the disintegration properties of tablets in opaque media using texture analysis.
Tablet disintegration characterisation is used in pharmaceutical research, development, and quality control. Standard methods used to characterise tablet disintegration are often dependent on visual observation in measurement of disintegration times. This presents a challenge for disintegration studies of tablets in opaque, physiologically relevant media that could be useful for tablet formulation optimisation. This study has explored an application of texture analysis disintegration testing, a non-visual, quantitative means of determining tablet disintegration end point, by analysing the disintegration behaviour of two tablet formulations in opaque media. In this study, the disintegration behaviour of one tablet formulation manufactured in-house, and Sybedia Flashtab placebo tablets in water, bovine, and human milk were characterised. A novel method is presented to characterise the disintegration process and to quantify the disintegration end points of the tablets in various media using load data generated by a texture analyser probe. The disintegration times in the different media were found to be statistically different (P<0.0001) from one another for both tablet formulations using one-way ANOVA. Using the Tukey post-hoc test, the Sybedia Flashtab placebo tablets were found not to have statistically significant disintegration times from each other in human versus bovine milk (adjusted P value 0.1685).This work was made possible through the generous support of the Saving Lives at Birth partners: the United States Agency for International Development (USAID), the Government of Norway, the Bill & Melinda Gates Foundation, Grand Challenges Canada and the UK Department for International Development (DFID).This is the accepted manuscript. The final version is available at http://www.sciencedirect.com/science/article/pii/S0378517315002392#
Chromatin Profiles of Chromosomally Integrated Human Herpesvirus-6A
Human herpesvirus-6A (HHV-6A) and 6B (HHV-6B) are two closely related betaherpesviruses that are associated with various diseases including seizures and encephalitis. The HHV-6A/B genomes have been shown to be present in an integrated state in the telomeres of latently infected cells. In addition, integration of HHV-6A/B in germ cells has resulted in individuals harboring this inherited chromosomally integrated HHV-6A/B (iciHHV-6) in every cell of their body. Until now, the viral transcriptome and the epigenetic modifications that contribute to the silencing of the integrated virus genome remain elusive. In the current study, we used a patient-derived iciHHV-6A cell line to assess the global viral gene expression profile by RNA-seq, and the chromatin profiles by MNase-seq and ChIP-seq analyses. In addition, we investigated an in vitro generated cell line (293-HHV-6A) that expresses GFP upon the addition of agents commonly used to induce herpesvirus reactivation such as TPA. No viral gene expression including miRNAs was detected from the HHV-6A genomes, indicating that the integrated virus is transcriptionally silent. Intriguingly, upon stimulation of the 293-HHV-6A cell line with TPA, only foreign promoters in the virus genome were activated, while all HHV-6A promoters remained completely silenced. The transcriptional silencing of latent HHV-6A was further supported by MNase-seq results, which demonstrate that the latent viral genome resides in a highly condensed nucleosome-associated state. We further explored the enrichment profiles of histone modifications via ChIP-seq analysis. Our results indicated that the HHV-6 genome is modestly enriched with the repressive histone marks H3K9me3/H3K27me3 and does not possess the active histone modifications H3K27ac/H3K4me3. Overall, these results indicate that HHV-6 genomes reside in a condensed chromatin state, providing insight into the epigenetic mechanisms associated with the silencing of the integrated HHV-6A genome
Numerical simulations of kink instability in line-tied coronal loops
The results from numerical simulations carried out using a new shock-capturing, Lagrangian-remap, 3D MHD code, Lare3d are presented. We study the evolution of the m=1 kink mode instability in a photospherically line-tied coronal loop that has no net axial current. During the non-linear evolution of the kink instability, large current concentrations develop in the neighbourhood of the infinite length mode rational surface. We investigate whether this strong current saturates at a finite value or whether scaling indicates current sheet formation. In particular, we consider the effect of the shear, defined by where is the fieldline twist of the loop, on the current concentration. We also include a non-uniform resistivity in the simulations and observe the amount of free magnetic energy released by magnetic reconnection
Public perceptions of a radioactively contaminated site: concerns, remediation preferences, and desired involvement.
A public attitudes survey was conducted in neighborhoods adjacent to a radioactively contaminated site whose remediation is now under the auspices of the U.S. Department of Energy's Formerly Utilized Sites Remedial Action Program (FUSRAP). The survey's purpose was to ascertain levels of actual and desired public involvement in the remediation process; to identify health, environmental, economic, and future land-use concerns associated with the site; and to solicit remediation strategy preferences. Surface water and groundwater contamination, desire for public involvement, and potential health risks were found to be the most highly ranked site concerns. Preferred remediation strategies included treatment of contaminated soil and excavation with off-site disposal. Among on-site remediation strategies, only institutional controls that leave the site undisturbed and do not require additional excavation of materials were viewed favorably. Cost of remediation appeared to influence remediation strategy preference; however, no strategy was viewed as a panacea. Respondents were also concerned with protecting future generations, better assessment of risks to health and the environment, and avoiding generation of additional contaminated materials
Crystal Structure of Human AKT1 with an Allosteric Inhibitor Reveals a New Mode of Kinase Inhibition
AKT1 (NP_005154.2) is a member of the serine/threonine AGC protein kinase family involved in cellular metabolism, growth, proliferation and survival. The three human AKT isozymes are highly homologous multi-domain proteins with both overlapping and distinct cellular functions. Dysregulation of the AKT pathway has been identified in multiple human cancers. Several clinical trials are in progress to test the efficacy of AKT pathway inhibitors in treating cancer. Recently, a series of AKT isozyme-selective allosteric inhibitors have been reported. They require the presence of both the pleckstrin-homology (PH) and kinase domains of AKT, but their binding mode has not yet been elucidated. We present here a 2.7 Ă… resolution co-crystal structure of human AKT1 containing both the PH and kinase domains with a selective allosteric inhibitor bound in the interface. The structure reveals the interactions between the PH and kinase domains, as well as the critical amino residues that mediate binding of the inhibitor to AKT1. Our work also reveals an intricate balance in the enzymatic regulation of AKT, where the PH domain appears to lock the kinase in an inactive conformation and the kinase domain disrupts the phospholipid binding site of the PH domain. This information advances our knowledge in AKT1 structure and regulation, thereby providing a structural foundation for interpreting the effects of different classes of AKT inhibitors and designing selective ones
Drawing the Line: How African, Caribbean and White British Women Live Out Psychologically Abusive Experiences
The final, definitive version of this paper has been published in Violence Against Women, 19 (9):1104-32, Sept 2013 by SAGE Publications Ltd, All rights reserved. © The Author(s) 2013.
The online version of this article can be found at: http://vaw.sagepub.com/content/19/9/110
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