7,614 research outputs found
Recommended from our members
High-resolution mapping of fluoroquinolones in TB rabbit lesions reveals specific distribution in immune cell types.
Understanding the distribution patterns of antibiotics at the site of infection is paramount to selecting adequate drug regimens and developing new antibiotics. Tuberculosis (TB) lung lesions are made of various immune cell types, some of which harbor persistent forms of the pathogen, Mycobacterium tuberculosis. By combining high resolution MALDI MSI with histology staining and quantitative image analysis in rabbits with active TB, we have mapped the distribution of a fluoroquinolone at high resolution, and identified the immune-pathological factors driving its heterogeneous penetration within TB lesions, in relation to where bacteria reside. We find that macrophage content, distance from lesion border and extent of necrosis drive the uneven fluoroquinolone penetration. Preferential uptake in macrophages and foamy macrophages, where persistent bacilli reside, compared to other immune cells present in TB granulomas, was recapitulated in vitro using primary human cells. A nonlinear modeling approach was developed to help predict the observed drug behavior in TB lesions. This work constitutes a methodological advance for the co-localization of drugs and infectious agents at high spatial resolution in diseased tissues, which can be applied to other diseases with complex immunopathology
The motion of a deforming capsule through a corner
A three-dimensional deformable capsule convected through a square duct with a
corner is studied via numerical simulations. We develop an accelerated boundary
integral implementation adapted to general geometries and boundary conditions.
A global spectral method is adopted to resolve the dynamics of the capsule
membrane developing elastic tension according to the neo-Hookean constitutive
law and bending moments in an inertialess flow. The simulations show that the
trajectory of the capsule closely follows the underlying streamlines
independently of the capillary number. The membrane deformability, on the other
hand, significantly influences the relative area variations, the advection
velocity and the principal tensions observed during the capsule motion. The
evolution of the capsule velocity displays a loss of the time-reversal symmetry
of Stokes flow due to the elasticity of the membrane. The velocity decreases
while the capsule is approaching the corner as the background flow does,
reaches a minimum at the corner and displays an overshoot past the corner due
to the streamwise elongation induced by the flow acceleration in the downstream
branch. This velocity overshoot increases with confinement while the maxima of
the major principal tension increase linearly with the inverse of the duct
width. Finally, the deformation and tension of the capsule are shown to
decrease in a curved corner
Phase transitions during fruiting body formation in Myxococcus xanthus
The formation of a collectively moving group benefits individuals within a
population in a variety of ways such as ultra-sensitivity to perturbation,
collective modes of feeding, and protection from environmental stress. While
some collective groups use a single organizing principle, others can
dynamically shift the behavior of the group by modifying the interaction rules
at the individual level. The surface-dwelling bacterium Myxococcus xanthus
forms dynamic collective groups both to feed on prey and to aggregate during
times of starvation. The latter behavior, termed fruiting-body formation,
involves a complex, coordinated series of density changes that ultimately lead
to three-dimensional aggregates comprising hundreds of thousands of cells and
spores. This multi-step developmental process most likely involves several
different single-celled behaviors as the population condenses from a loose,
two-dimensional sheet to a three-dimensional mound. Here, we use
high-resolution microscopy and computer vision software to spatiotemporally
track the motion of thousands of individuals during the initial stages of
fruiting body formation. We find that a combination of cell-contact-mediated
alignment and internal timing mechanisms drive a phase transition from
exploratory flocking, in which cell groups move rapidly and coherently over
long distances, to a reversal-mediated localization into streams, which act as
slow-spreading, quasi-one-dimensional nematic fluids. These observations lead
us to an active liquid crystal description of the myxobacterial development
cycle.Comment: 16 pages, 5 figure
Computational estimation of haemodynamics and tissue stresses in abdominal aortic aneurysms
'o e Abdominal aortic aneurysm is a vascular disease involving a focal dilation of the aorta. The exact cause is unknown but possibilities include infection and weakening of the connective tissue. Risk factors include a history of atherosclerosis, current smoking and a close relative with the disease. Although abdominal aortic aneurysm can affect anyone, it is most often seen in older men, and may be present in up to 5.9 % of the population aged 80 years. Biomechanical factors such as tissue stresses and shear stresses have been shown to play a part in aneurysm progression, although the specific mechanisms are still to be determined. The growth rate of the abdominal aortic aneurysm has been found to correlate with the peak stress in the aneurysm wall and the blood flow is thought to influence disease development. In order to resolve the connections between biology and biomechanics, accurate estimations of the forces involved are required. The first part of this thesis assesses the use of computational fluid dynamics for modelling haemodynamics in abdominal aortic aneurysms. Boundary conditions from the literature o
- …