191 research outputs found
Lung injury after cigarette smoking is particle related
The specific component responsible and the mechanistic pathway for increased human morbidity and mortality after cigarette smoking are yet to be delineated. We propose that 1) injury and disease following cigarette smoking are associated with exposure to and retention of particles produced during smoking and 2) the biological effects of particles associated with cigarette smoking share a single mechanism of injury with all particles. Smoking one cigarette exposes the human respiratory tract to between 15,000 and 40,000 μg particulate matter; this is a carbonaceous product of an incomplete combustion. There are numerous human exposures to other particles, and these vary widely in composition, absolute magnitude, and size of the particle. Individuals exposed to all these particles share a common clinical presentation with a loss of pulmonary function, increased bronchial hyperresponsiveness, pathologic changes of emphysema and fibrosis, and comorbidities, including cardiovascular disease, cerebrovascular disease, peripheral vascular disease, and cancers. Mechanistically, all particle exposures produce an oxidative stress, which is associated with a series of reactions, including an activation of kinase cascades and transcription factors, release of inflammatory mediators, and apoptosis. If disease associated with cigarette smoking is recognized to be particle related, then certain aspects of the clinical presentation can be predicted; this would include worsening of pulmonary function and progression of pathological changes and comorbidity (eg, emphysema and carcinogenesis) after smoking cessation since the particle is retained in the lung and the exposure continues
Emerging Risk Profile of Lung Cancer Therapy: Diffuse Alveolar Hemorrhage from Osimertinib
Osimertinib is an oral epithelial growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) used primarily in the treatment of metastatic non-small cell lung cancer. It is usually well tolerated with less than 5% of patients developing significant pulmonary toxicity from the medication, typically within the first few months after initiation. Previously reported pulmonary adverse reactions include pneumonitis (nonspecific interstitial pneumonia or other forms of acute interstitial process), fleeting asymptomatic infiltrates on imaging, and eosinophilic pneumonia. We present an interesting case of a 65-year-old female with recurrent metastatic adenocarcinoma of the lung, treated with Osimertinib for 4 months, who developed a previously unreported toxicity of diffuse alveolar hemorrhage (DAH) requiring mechanical ventilatory support
Birkman Screening and the Covariance of the Fluid Velocity of Fixed Beds
The phenomenon of Brinkman screening, whereby the fluid velocity disturbance produced by each particle in a fixed bed is attenuated by the forces that the fluid exerts on surrounding particles, plays a crucial role in limiting the range of velocity correlations in porous media and fixed beds. Koch and Brady [J. Fluid Mech. 154, 399 (1985)] showed theoretically that Brinkman screening leads to a finite hydrodynamic diffusion coefficient for fluid phase tracers in dilute fixed beds. In this Letter, we present the results of two simulation techniques (lattice-Boltzmann method and a multipole method) confirming the screening of the fluid velocity covariance that underlies the Koch and Brady theory
Identification and Modeling the Impact of Marine Shale Bedrock on Groundwater and Stream Salinity: Upper Colorado River Basin
Recent studies have shown that groundwater is a major contributor to stream salinity in the Upper Colorado River Basin. The primary salt sources are the marine shales and shale residuum that underlie the soils of much of the basin. A field site in the Price River Basin, a tributary to the Green and Colorado Rivers, was selected to study the physical and chemical factors that control the interactions between groundwater and these shales. Preliminary data were available at the site as a result of a Bureau of Reclamation study conducted by CH2M Hill. On the basis of the CH2M Hill study and the additional data collected during this study groundwater flow paths, salt transport and weathering processes were identified. Results show that the groundwater evolved from a calcium-bicarbonate water to a sodium-sulfate water with depth and distance along the flow paths. Geochemical equilibrium modeling and mass balance computations were performed using the USGS models PHREEQE and BALANCE. A preliminary saturated-unsaturated two-dimensional flow model (UNSAT) was implemented along the identified groundwater flow path. Once a satisfactory flow calibration was achieved, a solute transport model was then implemented to examine the relative importance of advective, dispersive and diffusive mixing processes along the flow profile. Preliminary management runs were made to study the effect of possible changes in land use practices. Results of these hypothetical cases suggest that water conservation methods (improved irrigation efficiency, canal lining and retiring irrigated land) will reduce return flow salt loads over the short run (about 50 years), when the transport of salts by displacement is most important. However, these salinity control alternatives are much less effective in the long range (\u3e 50 years) because the diffuse salt loading from underlying marine shales is unaffected by groundwater flow rates in the alluvium. Although additional field data must be collected for verification the proposed model is a realistic first step towards a quantitative physically based approach to land use-salinity control issues
Steady Stokes flow with long-range correlations, fractal Fourier spectrum, and anomalous transport
We consider viscous two-dimensional steady flows of incompressible fluids
past doubly periodic arrays of solid obstacles. In a class of such flows, the
autocorrelations for the Lagrangian observables decay in accordance with the
power law, and the Fourier spectrum is neither discrete nor absolutely
continuous. We demonstrate that spreading of the droplet of tracers in such
flows is anomalously fast. Since the flow is equivalent to the integrable
Hamiltonian system with 1 degree of freedom, this provides an example of
integrable dynamics with long-range correlations, fractal power spectrum, and
anomalous transport properties.Comment: 4 pages, 4 figures, published in Physical Review Letter
Far-field approximation for hydrodynamic interactions in parallel-wall geometry
A complete analysis is presented for the far-field creeping flow produced by
a multipolar force distribution in a fluid confined between two parallel planar
walls. We show that at distances larger than several wall separations the flow
field assumes the Hele-Shaw form, i.e., it is parallel to the walls and varies
quadratically in the transverse direction. The associated pressure field is a
two-dimensional harmonic function that is characterized by the same multipolar
number m as the original force multipole. Using these results we derive
asymptotic expressions for the Green's matrix that represents Stokes flow in
the wall-bounded fluid in terms of a multipolar spherical basis. This Green's
matrix plays a central role in our recently proposed algorithm [Physica A xx,
{\bf xxx} (2005)] for evaluating many-body hydrodynamic interactions in a
suspension of spherical particles in the parallel-wall geometry. Implementation
of our asymptotic expressions in this algorithm increases its efficiency
substantially because the numerically expensive evaluation of the exact matrix
elements is needed only for the neighboring particles. Our asymptotic analysis
will also be useful in developing hydrodynamic algorithms for wall-bounded
periodic systems and implementing acceleration methods by using corresponding
results for the two-dimensional scalar potential.Comment: 28 pages 5 figure
Many-particle hydrodynamic interactions in parallel-wall geometry: Cartesian-representation method
This paper describes the results of our theoretical and numerical studies of
hydrodynamic interactions in a suspension of spherical particles confined
between two parallel planar walls, under creeping-flow conditions. We propose a
novel algorithm for accurate evaluation of the many-particle friction matrix in
this system--no such algorithm has been available so far.
Our approach involves expanding the fluid velocity field into spherical and
Cartesian fundamental sets of Stokes flows. The interaction of the fluid with
the particles is described using the spherical basis fields; the flow scattered
with the walls is expressed in terms of the Cartesian fundamental solutions. At
the core of our method are transformation relations between the spherical and
Cartesian basis sets. These transformations allow us to describe the flow field
in a system that involves both the walls and particles.
We used our accurate numerical results to test the single-wall superposition
approximation for the hydrodynamic friction matrix. The approximation yields
fair results for quantities dominated by single particle contributions, but it
fails to describe collective phenomena, such as a large transverse resistance
coefficient for linear arrays of spheres
Simulating Three-Dimensional Hydrodynamics on a Cellular-Automata Machine
We demonstrate how three-dimensional fluid flow simulations can be carried
out on the Cellular Automata Machine 8 (CAM-8), a special-purpose computer for
cellular-automata computations. The principal algorithmic innovation is the use
of a lattice-gas model with a 16-bit collision operator that is specially
adapted to the machine architecture. It is shown how the collision rules can be
optimized to obtain a low viscosity of the fluid. Predictions of the viscosity
based on a Boltzmann approximation agree well with measurements of the
viscosity made on CAM-8. Several test simulations of flows in simple geometries
-- channels, pipes, and a cubic array of spheres -- are carried out.
Measurements of average flux in these geometries compare well with theoretical
predictions.Comment: 19 pages, REVTeX and epsf macros require
Free energy of colloidal particles at the surface of sessile drops
The influence of finite system size on the free energy of a spherical
particle floating at the surface of a sessile droplet is studied both
analytically and numerically. In the special case that the contact angle at the
substrate equals a capillary analogue of the method of images is
applied in order to calculate small deformations of the droplet shape if an
external force is applied to the particle. The type of boundary conditions for
the droplet shape at the substrate determines the sign of the capillary
monopole associated with the image particle. Therefore, the free energy of the
particle, which is proportional to the interaction energy of the original
particle with its image, can be of either sign, too. The analytic solutions,
given by the Green's function of the capillary equation, are constructed such
that the condition of the forces acting on the droplet being balanced and of
the volume constraint are fulfilled. Besides the known phenomena of attraction
of a particle to a free contact line and repulsion from a pinned one, we
observe a local free energy minimum for the particle being located at the drop
apex or at an intermediate angle, respectively. This peculiarity can be traced
back to a non-monotonic behavior of the Green's function, which reflects the
interplay between the deformations of the droplet shape and the volume
constraint.Comment: 24 pages, 19 figure
Meta-analysis Reveals Genome-Wide Significance at 15q13 for Nonsyndromic Clefting of Both the Lip and the Palate, and Functional Analyses Implicate GREM1 As a Plausible Causative Gene
Nonsyndromic orofacial clefts are common birth defects with multifactorial etiology. The
most common type is cleft lip, which occurs with or without cleft palate (nsCLP and nsCLO,
respectively). Although genetic components play an important role in nsCLP, the genetic
factors that predispose to palate involvement are largely unknown. In this study, we carried
out a meta-analysis on genetic and clinical data from three large cohorts and identified
strong association between a region on chromosome 15q13 and nsCLP (P = 8.13×10−14 for
rs1258763; relative risk (RR): 1.46, 95% confidence interval (CI): 1.32–1.61)) but not
nsCLO (P = 0.27; RR: 1.09 (0.94–1.27)). The 5 kb region of strongest association maps
downstream of Gremlin-1 (GREM1), which encodes a secreted antagonist of the BMP4
pathway. We show during mouse embryogenesis, Grem1 is expressed in the developing lip
and soft palate but not in the hard palate. This is consistent with genotype-phenotype correlations
between rs1258763 and a specific nsCLP subphenotype, since a more than two-fold
increase in risk was observed in patients displaying clefts of both the lip and soft palate but
who had an intact hard palate (RR: 3.76, CI: 1.47–9.61, Pdiff<0.05). While we did not find lip
or palate defects in Grem1-deficient mice, wild type embryonic palatal shelves developed
divergent shapes when cultured in the presence of ectopic Grem1 protein (P = 0.0014). The
present study identified a non-coding region at 15q13 as the second, genome-wide significant
locus specific for nsCLP, after 13q31. Moreover, our data suggest that the closely
located GREM1 gene contributes to a rare clinical nsCLP entity. This entity specifically
involves abnormalities of the lip and soft palate, which develop at different time-points and
in separate anatomical regions.Clefts of the lip and palate are common birth defects, and require long-term multidisciplinary
management. Their etiology involves genetic factors and environmental influences
and/or a combination of both, however, these interactions are poorly defined. Moreover,
although clefts of the lip may or may not involve the palate, the determinants predisposing
to specific subphenotypes are largely unknown. Here we demonstrate that variations in
the non-coding region near the GREM1 gene show a highly significant association with a
particular phenotype in which cleft lip and cleft palate co-occ
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