600 research outputs found
Effect of vertical active vibration isolation on tracking performance and on ride qualities
An investigation to determine the effect on pilot performance and comfort of an active vibration isolation system for a commercial transport pilot seat is reported. The test setup consisted of: a hydraulic shaker which produced random vertical vibration inputs; the active vibration isolation system; the pilot seat; the pilot control wheel and column; the side-arm controller; and a two-axis compensatory tracking task. The effects of various degrees of pilot isolation on short-term (two-minute) tracking performance and comfort were determined
Microscopic Surface Structure of Liquid Alkali Metals
We report an x-ray scattering study of the microscopic structure of the
surface of a liquid alkali metal. The bulk liquid structure factor of the
eutectic K67Na33 alloy is characteristic of an ideal mixture, and so shares the
properties of an elemental liquid alkali metal. Analysis of off-specular
diffuse scattering and specular x-ray reflectivity shows that the surface
roughness of the K-Na alloy follows simple capillary wave behavior with a
surface structure factor indicative of surface induced layering. Comparison of
thelow-angle tail of the K67Na33 surface structure factor with the one measured
for liquid Ga and In previously suggests that layering is less pronounced in
alkali metals. Controlled exposure of the liquid to H2 and O2 gas does not
affect the surface structure, indicating that oxide and hydride are not stable
at the liquid surface under these experimental conditions.Comment: 12 pages, 3 figures, published in Phys. Rev.
Commercializing Biomedical Research Through Securitization Techniques
Biomedical innovation has become riskier, more expensive and more difficult to finance with traditional sources such as private and public equity. Here we propose a financial structure in which a large number of biomedical programs at various stages of development are funded by a single entity to substantially reduce the portfolio's risk. The portfolio entity can finance its activities by issuing debt, a critical advantage because a much larger pool of capital is available for investment in debt versus equity. By employing financial engineering techniques such as securitization, it can raise even greater amounts of more-patient capital. In a simulation using historical data for new molecular entities in oncology from 1990 to 2011, we find that megafunds of $5–15 billion may yield average investment returns of 8.9–11.4% for equity holders and 5–8% for 'research-backed obligation' holders, which are lower than typical venture-capital hurdle rates but attractive to pension funds, insurance companies and other large institutional investors
Regulatory and market influences on innovation pathways for the development of new antimicrobial drugs
Examining the role of sphingosine kinase-2 in the regulation of endothelial cell barrier integrity
A key mediator of vascular EC barrier integrity, S1P, is derived from phosphorylation of sphingosine by the SK-1 and SK-2. While previous work indicates that SK-1 can regulate EC barrier integrity, whether SK-2 has a similar role remains to be determined.A cell impedance assay was used to assess human umbilical vein EC and bone marrow EC barrier integrity in vitro, with application of the SK inhibitors ABC294640, PF543, SKi, and MP-A08. In vivo studies were conducted using intravital microscopy to assess EC barrier integrity in SK-1 (Sphk1(-/-) ) and SK-2 (Sphk2(-/-) ) knock-out mice.Only ABC294640 and MP-A08, which can both inhibit SK-2, caused a decrease in EC barrier integrity in vitro in both cell types. Intravital microscopy revealed that Sphk1(-/-) mice had reduced EC barrier integrity compared to WT mice, whereas no change was evident in Sphk2(-/-) mice.Our data suggest that in vitro inhibition of SK-2, can compromise the integrity of the EC monolayer, while SK-1 exerts a more dominant control in vivo. These data may have clinical implications and could aid in the development of new treatments for disorders of vascular barrier function.David P. Dimasi, Stuart M. Pitson, and Claudine S. Bonde
Anomalous layering at the liquid Sn surface
X-ray reflectivity measurements on the free surface of liquid Sn are
presented. They exhibit the high-angle peak, indicative of surface-induced
layering, also found for other pure liquid metals (Hg, Ga and In). However, a
low-angle peak, not hitherto observed for any pure liquid metal, is also found,
indicating the presence of a high-density surface layer. Fluorescence and
resonant reflectivity measurements rule out the assignment of this layer to
surface-segregation of impurities. The reflectivity is modelled well by a 10%
contraction of the spacing between the first and second atomic surface layers,
relative to that of subsequent layers. Possible reasons for this are discussed.Comment: 8 pages, 9 figures; to be submitted to Phys. Rev. B; updated
references, expanded discussio
Local and global modes of drug action in biochemical networks
It becomes increasingly accepted that a shift is needed from the traditional target-based approach of drug development to an integrated perspective of drug action in biochemical systems. We here present an integrative analysis of the interactions between drugs and metabolism based on the concept of drug scope. The drug scope represents the set of metabolic compounds and reactions that are potentially affected by a drug. We constructed and analyzed the scopes of all US approved drugs having metabolic targets. Our analysis shows that the distribution of drug scopes is highly uneven, and that drugs can be classified into several categories based on their scopes. Some of them have small scopes corresponding to localized action, while others have large scopes corresponding to potential large-scale systemic action. These groups are well conserved throughout different topologies of the underlying metabolic network. They can furthermore be associated to specific drug therapeutic properties
Charge density wave formation in Te (=Nd, Sm and Gd)
The rare earth () tellurides Te have a crystal structure
intermediate between that of Te and Te, consisting of alternating
single and double Te planes sandwiched between Te block layers. We have
successfully grown single crystals of NdTe, SmTe and
GdTe from a self flux, and describe here the first evidence for charge
density wave formation in these materials. The superlattice patterns for all
three compounds are relatively complex, consisting at room temperature of at
least two independent wavevectors. Consideration of the electronic structure
indicates that to a large extent these wave vectors are separately associated
with sheets of the Fermi surface which are principally derived from the single
and double Te layers.Comment: 10 pages, 6 figure
Economic Implications of Potential Changes to Regulatory and Reimbursement Policies for Medical Devices
Efficacious, effective, and embedded interventions: Implementation research in infectious disease control
Background: Research in infectious disease control is heavily skewed towards high end
technology; development of new drugs, vaccines and clinical interventions. Oft ignored, is the
evidence to inform the best strategies that ensure the embedding of interventions into health
systems and amongst populations. In this paper we undertake an analysis of the challenge in the
development of research for the sustainable implementation of disease control interventions.
Results: We highlight the fundamental differences between the research paradigms associated
with the development of technologies and interventions for disease control on the one hand and the research paradigms required for enhancing the sustainable uptake of those very same
interventions within the communities on the other. We provide a definition for implementation
research in an attempt to underscore its critical role and explore the multidisciplinary science
needed to address the challenges in disease control.
Conclusion: The greatest value for money in health research lies in the sustainable and effective implementation of already proven, efficacious solutions. The development of implementation research that can help provide some solutions on how this can be achieved is sorely needed
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