Pluripotency factors functionally premark cell-type-restricted enhancers in ES cells.

Enhancers for embryonic stem (ES) cell-expressed genes and lineage-determining factors are characterized by conventional marks of enhancer activation in ES cells1-3, but it remains unclear whether enhancers destined to regulate cell-type-restricted transcription units might also have distinct signatures in ES cells. Here we show that cell-type-restricted enhancers are 'premarked' and activated as transcription units by the binding of one or two ES cell transcription factors, although they do not exhibit traditional enhancer epigenetic marks in ES cells, thus uncovering the initial temporal origins of cell-type-restricted enhancers. This premarking is required for future cell-type-restricted enhancer activity in the differentiated cells, with the strength of the ES cell signature being functionally important for the subsequent robustness of cell-type-restricted enhancer activation. We have experimentally validated this model in macrophage-restricted enhancers and neural precursor cell (NPC)-restricted enhancers using ES cell-derived macrophages or NPCs, edited to contain specific ES cell transcription factor motif deletions. DNA hydroxyl-methylation of enhancers in ES cells, determined by ES cell transcription factors, may serve as a potential molecular memory for subsequent enhancer activation in mature macrophages. These findings suggest that the massive repertoire of cell-type-restricted enhancers are essentially hierarchically and obligatorily premarked by binding of a defining ES cell transcription factor in ES cells, dictating the robustness of enhancer activation in mature cells

Microencapsulation As A Potential Control Technique Against Sabellid Worms In Abalone Culture

We have developed a novel application for lipid-walled microcapsules (LWMs) in the potential control of sabellid infestations in abalone aquaculture. The use of LWMs takes advantage of the filter-feeding nature of the worms, versus the herbivory of the host abalone. Initial observations indicated that the pest was capable of feeding on particles ranging from 3-30 mu m in size. Lipid-walled microcapsules were prepared using different combinations of lipids (tristearin, tripalmitin, and fish oil) to encapsulate water-based solutions. Feeding experiments using worm-infested shells indicated that in a relatively short time (30-60 min) most of the worms (80-95%) fed on the LWMs and that large numbers of LWMs were ingested. Fecal pellets containing LWMs were observed in the rectums of worms within 15-30 min. Feeding efficiency was examined using different concentrations of LWMs. The sabellid worm was an efficient feeder. At low particle densities (2.6 x 10(4) particles/mL), 66.7% of the worms had eaten modest levels of LWMs. An asymptote in particle density in relation to feeding occurred at 2.6 x 10(5) particles/mL, with 83% of the worms feeding on large numbers of particles. In separate observations, LWMs composed of tripalmitin and fish oil were observed in various stages of digestion in the stomach, rectum, and fecal pellets of the worms. Microcapsules were also observed in the digestive tract of mud worms, Polydora spp. that were also inhabiting abalone shell. The utility of LWMs for delivery of toxins to the sabellid pest holds much promise in ridding the industry of this nuisance species

HoxA9 binds and represses the Cebpa +8 kb enhancer

C/EBPα plays a key role in specifying myeloid lineage development. HoxA9 is expressed in myeloid progenitors, with its level diminishing during myeloid maturation, and HOXA9 is over-expressed in a majority of acute myeloid leukemia cases, including those expressing NUP98-HOXD13. The objective of this study was to determine whether HoxA9 directly represses Cebpa gene expression. We find 4-fold increased HoxA9 and 5-fold reduced Cebpa in marrow common myeloid and LSK progenitors from Vav-NUP98-HOXD13 transgenic mice. Conversely, HoxA9 decreases 5-fold while Cebpa increases during granulocytic differentiation of 32Dcl3 myeloid cells. Activation of exogenous HoxA9-ER in 32Dcl3 cells reduces Cebpa mRNA even in the presence of cycloheximide, suggesting direct repression. Cebpa transcription in murine myeloid cells is regulated by a hematopoietic-specific +37 kb enhancer and by a more widely active +8 kb enhancer. ChIP-Seq analysis of primary myeloid progenitor cells expressing exogenous HoxA9 or HoxA9-ER demonstrates that HoxA9 localizes to both the +8 kb and +37 kb Cebpa enhancers. Gel shift analysis demonstrates HoxA9 binding to three consensus sites in the +8 kb enhancer, but no affinity for the single near-consensus site present in the +37 kb enhancer. Activity of a Cebpa +8 kb enhancer/promoter-luciferase reporter in 32Dcl3 or MOLM14 myeloid cells is increased ~2-fold by mutation of its three HOXA9-binding sites, suggesting that endogenous HoxA9 represses +8 kb Cebpa enhancer activity. In contrast, mutation of five C/EBPα-binding sites in the +8 kb enhancer reduces activity 3-fold. Finally, expression of a +37 kb enhancer/promoter-hCD4 transgene reporter is reduced ~2-fold in marrow common myeloid progenitors when the Vav-NUP98-HOXD13 transgene is introduced. Overall, these data support the conclusion that HoxA9 represses Cebpa expression, at least in part via inhibition of its +8 kb enhancer, potentially allowing normal myeloid progenitors to maintain immaturity and contributing to the pathogenesis of acute myeloid leukemia associated with increased HOXA9

Strange Particles in Dense Matter and Kaon Condensates

We discuss the role of strangeness in dense matter and especially in neutron stars. The early (in density) introduction of hyperons found in many calculations is probably delayed by the decrease in vector mean field acting on the neutron. The decrease results from both conventional many-body rescattering effects and from the movement towards asymptotic freedom at high densities. Subthreshold $K^-$-meson production by the KaoS collaboration at GSI shows that the $K^-$-mass must be substantially lowered, by $\gtrsim$ 200 MeV at $\rho\sim 2\rho_0$. It is shown that explicit chiral symmetry breaking through the kaon mass may be responsible for $\Sigma^-$-nucleon and $\Xi^-$-nucleon scalar attraction being weaker than obtained by simple quark scaling. The normal mode of the strangeness minus, charge $e^-$, excitation is constructed as a linear combination of $K^-$-meson and $\Sigma^-$, neutron-hole state. Except for zero momentum, where the terms are unmixed the "kaesobar" is a linear combination of these two components.Comment: 10 pages, 8 postscript figures, Talk given at the International Conference on Hypernuclear and Strange Particle Physics (HYP97), Brookhaven Nat'l Lab., USA, October 13-18, 1997, to be published in Nucl. Phys.

A comparison of nursing tasks undertaken by regulated nurses and nursing support workers: a work sampling study

© 2016 John Wiley & Sons Ltd Aims: The aim of this study was to determine which tasks unregulated nursing support staff spend their work time undertaking and to determine differences between the work undertaken by licensed/regulated nurses on units which have nursing support workers and those on units which do not. Background: Acute hospital nursing teams often include nursing support staff; little is known about what kinds of tasks these unregulated support workers do and how it affects the work tasks of their licensed/regulated team members. Design: Cross-sectional analysis of nurse work sampling data. Methods: Data collection took place between March–October 2013. The proportion of time spent on 25 work activities by nursing support staff and licensed/regulated nursing staff was compared. Logistic regression models estimated whether nursing support staff or licensed/regulated nurses were more likely to conduct direct and indirect patient care tasks and whether licensed/regulated nurses on units with nursing support staff were more likely to conduct direct or indirect tasks compared with those on units without nursing support workers. Results: Nursing support staff spent the majority of their time engaged in direct care tasks, e.g. admission and assessment, hygiene and mobility. Although licensed/regulated nurses were less likely to undertake direct care tasks compared with support workers, those who worked on units with support workers undertook more direct care compared with those who worked on units without support workers. Conclusions: Nursing support workers were given tasks that required substantial amounts of patient interaction. These staff may be associated with an increase in direct care tasks for licensed/regulated nurses, who may duplicate the direct care done by nursing support workers

Paying for Likes? Understanding Facebook like fraud using honeypots

Facebook pages offer an easy way to reach out to a very large audience as they can easily be promoted using Facebook's advertising platform. Recently, the number of likes of a Facebook page has become a measure of its popularity and profitability, and an underground market of services boosting page likes, aka like farms, has emerged. Some reports have suggested that like farms use a network of profiles that also like other pages to elude fraud protection algorithms, however, to the best of our knowledge, there has been no systematic analysis of Facebook pages' promotion methods. This paper presents a comparative measurement study of page likes garnered via Facebook ads and by a few like farms. We deploy a set of honeypot pages, promote them using both methods, and analyze garnered likes based on likers' demographic, temporal, and social characteristics. We highlight a few interesting findings, including that some farms seem to be operated by bots and do not really try to hide the nature of their operations, while others follow a stealthier approach, mimicking regular users' behavior

Explicit solution for vibrating bar with viscous boundaries and internal damper

We investigate longitudinal vibrations of a bar subjected to viscous boundary conditions at each end, and an internal damper at an arbitrary point along the bar's length. The system is described by four independent parameters and exhibits a variety of behaviors including rigid motion, super stability/instability and zero damping. The solution is obtained by applying the Laplace transform to the equation of motion and computing the Green's function of the transformed problem. This leads to an unconventional eigenvalue-like problem with the spectral variable in the boundary conditions. The eigenmodes of the problem are necessarily complex-valued and are not orthogonal in the usual inner product. Nonetheless, in generic cases we obtain an explicit eigenmode expansion for the response of the bar to initial conditions and external force. For some special values of parameters the system of eigenmodes may become incomplete, or no non-trivial eigenmodes may exist at all. We thoroughly analyze physical and mathematical reasons for this behavior and explicitly identify the corresponding parameter values. In particular, when no eigenmodes exist, we obtain closed form solutions. Theoretical analysis is complemented by numerical simulations, and analytic solutions are compared to computations using finite elements.Comment: 29 pages, 6 figure

Cost-sensitive Bayesian network learning using sampling

A significant advance in recent years has been the development of cost-sensitive decision tree learners, recognising that real world classification problems need to take account of costs of misclassification and not just focus on accuracy. The literature contains well over 50 cost-sensitive decision tree induction algorithms, each with varying performance profiles. Obtaining good Bayesian networks can be challenging and hence several algorithms have been proposed for learning their structure and parameters from data. However, most of these algorithms focus on learning Bayesian networks that aim to maximise the accuracy of classifications. Hence an obvious question that arises is whether it is possible to develop cost-sensitive Bayesian networks and whether they would perform better than cost-sensitive decision trees for minimising classification cost? This paper explores this question by developing a new Bayesian network learning algorithm based on changing the data distribution to reflect the costs of misclassification. The proposed method is explored by conducting experiments on over 20 data sets. The results show that this approach produces good results in comparison to more complex cost-sensitive decision tree algorithms

Changes to nurses’ practice environment over time

© 2016 John Wiley & Sons Ltd Aims: To examine changes in the nursing practice environment, retention-related factors, unit stability and patient care tasks delayed or left undone, over two periods between 2004 and 2013. Background: Positive nurse practice environments have been linked to nurse retention and care quality outcomes. Methods: The collection of the Practice Environment Scale of the Nursing Work Index, job satisfaction, intent to leave, unit instability and tasks delayed or not done at six acute-care hospitals across three Australian states, in two waves between 2004 and 2013; results from the two waves are compared. Results: On average, practice environment scores declined slightly; nurses reported a greater difficulty in finding another nursing position, lower intent to leave their current job and greater instability in their current position. Rates of delayed tasks increased over the period, whereas rates of tasks left undone have decreased over the period. Conclusions: The decline in nurses’ perceptions of the quality of the practice environment is disappointing, particularly given the protracted workforce shortages that have persisted. Significant organisational restructuring and turnover of nurse executives may have contributed to this decline. Implication for Nursing Management: Managers need to apply existing evidence to improve nurse practice environments and manage instability