3,528 research outputs found
Korn's second inequality and geometric rigidity with mixed growth conditions
Geometric rigidity states that a gradient field which is -close to the
set of proper rotations is necessarily -close to a fixed rotation, and is
one key estimate in nonlinear elasticity. In several applications, as for
example in the theory of plasticity, energy densities with mixed growth appear.
We show here that geometric rigidity holds also in and in
interpolation spaces. As a first step we prove the corresponding linear
inequality, which generalizes Korn's inequality to these spaces
Search algorithms as a framework for the optimization of drug combinations
Combination therapies are often needed for effective clinical outcomes in the
management of complex diseases, but presently they are generally based on
empirical clinical experience. Here we suggest a novel application of search
algorithms, originally developed for digital communication, modified to
optimize combinations of therapeutic interventions. In biological experiments
measuring the restoration of the decline with age in heart function and
exercise capacity in Drosophila melanogaster, we found that search algorithms
correctly identified optimal combinations of four drugs with only one third of
the tests performed in a fully factorial search. In experiments identifying
combinations of three doses of up to six drugs for selective killing of human
cancer cells, search algorithms resulted in a highly significant enrichment of
selective combinations compared with random searches. In simulations using a
network model of cell death, we found that the search algorithms identified the
optimal combinations of 6-9 interventions in 80-90% of tests, compared with
15-30% for an equivalent random search. These findings suggest that modified
search algorithms from information theory have the potential to enhance the
discovery of novel therapeutic drug combinations. This report also helps to
frame a biomedical problem that will benefit from an interdisciplinary effort
and suggests a general strategy for its solution.Comment: 36 pages, 10 figures, revised versio
Heritability of Attractiveness to Mosquitoes
Female mosquitoes display preferences for certain individuals over others, which is determined by differences in volatile chemicals produced by the human body and detected by mosquitoes. Body odour can be controlled genetically but the existence of a genetic basis for differential attraction to insects has never been formally demonstrated. This study investigated heritability of attractiveness to mosquitoes by evaluating the response of Aedes aegypti (=Stegomyia aegypti) mosquitoes to odours from the hands of identical and non-identical twins in a dual-choice assay. Volatiles from individuals in an identical twin pair showed a high correlation in attractiveness to mosquitoes, while non-identical twin pairs showed a significantly lower correlation. Overall, there was a strong narrow-sense heritability of 0.62 (SE 0.124) for relative attraction and 0.67 (0.354) for flight activity based on the average of ten measurements. The results demonstrate an underlying genetic component detectable by mosquitoes through olfaction. Understanding the genetic basis for attractiveness could create a more informed approach to repellent development
The structure of a resuscitation-promoting factor domain from Mycobacterium tuberculosis shows homology to lysozymes
Resuscitation-promoting factor (RPF) proteins reactivate stationary-phase cultures of (G+C)-rich Gram-positive bacteria including the causative agent of tuberculosis, Mycobacterium tuberculosis. We report the solution structure of the RPF domain from M. tuberculosis Rv1009 (RpfB) solved by heteronuclear multidimensional NMR. Structural homology with various glycoside hydrolases suggested that RpfB cleaved oligosaccharides. Biochemical studies indicate that a conserved active site glutamate is important for resuscitation activity. These data, as well as the presence of a clear binding pocket for a large molecule, indicate that oligosaccharide cleavage is probably the signal for revival from dormancy
Three-dimensional femtosecond laser nanolithography of crystals
Nanostructuring hard optical crystals has so far been exclusively feasible at
their surface, as stress induced crack formation and propagation has rendered
high precision volume processes ineffective. We show that the inner chemical
etching reactivity of a crystal can be enhanced at the nanoscale by more than
five orders of magnitude by means of direct laser writing. The process allows
to produce cm-scale arbitrary three-dimensional nanostructures with 100 nm
feature sizes inside large crystals in absence of brittle fracture. To showcase
the unique potential of the technique, we fabricate photonic structures such as
sub-wavelength diffraction gratings and nanostructured optical waveguides
capable of sustaining sub-wavelength propagating modes inside yttrium aluminum
garnet crystals. This technique could enable the transfer of concepts from
nanophotonics to the fields of solid state lasers and crystal optics.Comment: Submitted Manuscript and Supplementary Informatio
MATRICS: A Method for Aggregating The Reporting of Interventions in Complex Studies
There are few rigorous methods for combining qualitative and quantitative findings from studies with complex interventions using multiple research methods and giving appropriate weight to each without introducing bias to the overall conclusions.We developed a Method for Aggregating The Reporting of Interventions in Complex Studies (MATRICS) for the ENIGMA study (Evaluating Innovations in Gastroenterology by the NHS Modernisation Agency) – a multi-centre, mixed-methods study to evaluate the impact of the Modernising Endoscopy Services programme [1], funded by the UK National Institute for Health Research (NIHR SDO ref 08/1304/46)
Selecting improved Lotus nodulating rhizobia to expedite the development of new forage species
Development of the preterm gut microbiome in twins at risk of necrotising enterocolitis and sepsis
The preterm gut microbiome is a complex dynamic community influenced by genetic and environmental factors and is implicated in the pathogenesis of necrotising enterocolitis (NEC) and sepsis. We aimed to explore the longitudinal development of the gut microbiome in preterm twins to determine how shared environmental and genetic factors may influence temporal changes and compared this to the expressed breast milk (EBM) microbiome. Stool samples (n = 173) from 27 infants (12 twin pairs and 1 triplet set) and EBM (n = 18) from 4 mothers were collected longitudinally. All samples underwent PCR-DGGE (denaturing gradient gel electrophoresis) analysis and a selected subset underwent 454 pyrosequencing. Stool and EBM shared a core microbiome dominated by Enterobacteriaceae, Enterococcaceae, and Staphylococcaceae. The gut microbiome showed greater similarity between siblings compared to unrelated individuals. Pyrosequencing revealed a reduction in diversity and increasing dominance of Escherichia sp. preceding NEC that was not observed in the healthy twin. Antibiotic treatment had a substantial effect on the gut microbiome, reducing Escherichia sp. and increasing other Enterobacteriaceae.
This study demonstrates related preterm twins share similar gut microbiome development, even within the complex environment of neonatal intensive care. This is likely a result of shared genetic and immunomodulatory factors as well as exposure to the same maternal microbiome during birth, skin contact and exposure to EBM. Environmental factors including antibiotic exposure and feeding are additional significant determinants of community structure, regardless of host genetics
Generation of Functional CLL-Specific Cord Blood CTL Using CD40-Ligated CLL APC
PMCID: PMC3526610This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Advancing Tests of Relativistic Gravity via Laser Ranging to Phobos
Phobos Laser Ranging (PLR) is a concept for a space mission designed to
advance tests of relativistic gravity in the solar system. PLR's primary
objective is to measure the curvature of space around the Sun, represented by
the Eddington parameter , with an accuracy of two parts in ,
thereby improving today's best result by two orders of magnitude. Other mission
goals include measurements of the time-rate-of-change of the gravitational
constant, and of the gravitational inverse square law at 1.5 AU
distances--with up to two orders-of-magnitude improvement for each. The science
parameters will be estimated using laser ranging measurements of the distance
between an Earth station and an active laser transponder on Phobos capable of
reaching mm-level range resolution. A transponder on Phobos sending 0.25 mJ, 10
ps pulses at 1 kHz, and receiving asynchronous 1 kHz pulses from earth via a 12
cm aperture will permit links that even at maximum range will exceed a photon
per second. A total measurement precision of 50 ps demands a few hundred
photons to average to 1 mm (3.3 ps) range precision. Existing satellite laser
ranging (SLR) facilities--with appropriate augmentation--may be able to
participate in PLR. Since Phobos' orbital period is about 8 hours, each
observatory is guaranteed visibility of the Phobos instrument every Earth day.
Given the current technology readiness level, PLR could be started in 2011 for
launch in 2016 for 3 years of science operations. We discuss the PLR's science
objectives, instrument, and mission design. We also present the details of
science simulations performed to support the mission's primary objectives.Comment: 25 pages, 10 figures, 9 table
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