11,078 research outputs found
The Effects of Crack Ellipticity on the Mode I SIFs of a Simulated Eroded Pressurized Cylinder
AbstractThe three dimensional stress intensity factors (3D SIFs) of a pressurized cylinder can be greatly affected by many factors. While an autofrettage process may introduce favorable residual stresses on the bore of the cylinder, other factors such as erosions and cracks, once introduced, may greatly reduce the effectiveness of the autofrettage. In this study, a closer look was given to problems with different crack configurations. Effort was expended to evaluate how the ellipticity of cracks affects the overall fatigue life of a simulated eroded pressurized cylinder in comparison with circular crack only configurations. Numerical analysis was performed using ANSYS, a standard commercially available finite element package. The residual stress due to any autofrettage process was simulated using the equivalent thermal loading. In-depth discussion was given to results when cracks of different ellipticity interact with other parameters including the depth of crack and the geometrical configurations of erosion. Specific cases considered include: crack ellipticity a/c=0.5, 1 and 1.5; relative crack depth a/t=0.01-0.2; relative erosion depth d/t=0.05; erosion relative finite length Le/L=0.12-1; erosion ellipticity d/h=0.3-2. Relevant non-erosion results are used for the sake of comparison
Rational Group Decision Making. A random field Ising model at T=0
A modified version of a finite random field Ising ferromagnetic model in an
external magnetic field at zero temperature is presented to describe group
decision making. Fields may have a non-zero average. A postulate of minimum
inter-individual conflicts is assumed. Interactions then produce a group
polarization along one very choice which is however randomly selected. A small
external social pressure is shown to have a drastic effect on the polarization.
Individual bias related to personal backgrounds, cultural values and past
experiences are introduced via quenched local competing fields. They are shown
to be instrumental in generating a larger spectrum of collective new choices
beyond initial ones. In particular, compromise is found to result from the
existence of individual competing bias. Conflict is shown to weaken group
polarization. The model yields new psycho-sociological insights about consensus
and compromise in groups.Comment: 25 pages, late
Mechanical control of the directional stepping dynamics of the kinesin motor
Among the multiple steps constituting the kinesin's mechanochemical cycle,
one of the most interesting events is observed when kinesins move an 8-nm step
from one microtubule (MT)-binding site to another. The stepping motion that
occurs within a relatively short time scale (~100 microsec) is, however, beyond
the resolution of current experiments, therefore a basic understanding to the
real-time dynamics within the 8-nm step is still lacking. For instance, the
rate of power stroke (or conformational change), that leads to the
undocked-to-docked transition of neck-linker, is not known, and the existence
of a substep during the 8-nm step still remains a controversial issue in the
kinesin community. By using explicit structures of the kinesin dimer and the MT
consisting of 13 protofilaments (PFs), we study the stepping dynamics with
varying rates of power stroke (kp). We estimate that 1/kp <~ 20 microsec to
avoid a substep in an averaged time trace. For a slow power stroke with 1/kp>20
microsec, the averaged time trace shows a substep that implies the existence of
a transient intermediate, which is reminiscent of a recent single molecule
experiment at high resolution. We identify the intermediate as a conformation
in which the tethered head is trapped in the sideway binding site of the
neighboring PF. We also find a partial unfolding (cracking) of the binding
motifs occurring at the transition state ensemble along the pathways prior to
binding between the kinesin and MT.Comment: 26 pages, 10 figure
Dimensional Crossover in the Effective Second Harmonic Generation of Films of Random Dielectrics
The effective nonlinear response of films of random composites consisting of
a binary composite with nonlinear particles randomly embedded in a linear host
is theoretically and numerically studied. A theoretical expression for the
effective second harmonic generation susceptibility, incorporating the
thickness of the film, is obtained by combining a modified effective-medium
approximation with the general expression for the effective second harmonic
generation susceptibility in a composite. The validity of the thoretical
results is tested against results obtained by numerical simulations on random
resistor networks. Numerical results are found to be well described by our
theory. The result implies that the effective-medium approximation provides a
convenient way for the estimation of the nonlinear response in films of random
dielectrics.Comment: 9 pages, 2 figures; accepted for publication in Phys. Rev.
-NMR of Isolated Li Implanted into a Thin Copper Film
Depth-controlled -NMR was used to study highly spin-polarized Li
in a Cu film of thickness 100 nm deposited onto a MgO substrate. The positive
Knight Shifts and spin relaxation data show that Li occupies two sites at
low temperatures, assigned to be the substitutional () and octahedral ()
interstitial sites. Between 50 to 100 K, there is a site change from to
. The temperature dependence of the Knight shifts and spin-lattice
relaxation rates at high temperatures, i.e. when all the Li are in the
site, is consistent with the Korringa Law for a simple metal.Comment: Accepted for publication in Phys. Rev.
Three patients with homozygous familial hypercholesterolemia: Genomic sequencing and kindred analysis.
BackgroundHomozygous Familial Hypercholesterolemia (HoFH) is an inherited recessive condition associated with extremely high levels of low-density lipoprotein (LDL) cholesterol in affected individuals. It is usually caused by homozygous or compound heterozygous functional mutations in the LDL receptor (LDLR). A number of mutations causing FH have been reported in literature and such genetic heterogeneity presents great challenges for disease diagnosis.ObjectiveWe aim to determine the likely genetic defects responsible for three cases of pediatric HoFH in two kindreds.MethodsWe applied whole exome sequencing (WES) on the two probands to determine the likely functional variants among candidate FH genes. We additionally applied 10x Genomics (10xG) Linked-Reads whole genome sequencing (WGS) on one of the kindreds to identify potentially deleterious structural variants (SVs) underlying HoFH. A PCR-based screening assay was also established to detect the LDLR structural variant in a cohort of 641 patients with elevated LDL.ResultsIn the Caucasian kindred, the FH homozygosity can be attributed to two compound heterozygous LDLR damaging variants, an exon 12 p.G592E missense mutation and a novel 3kb exon 1 deletion. By analyzing the 10xG phased data, we ascertained that this deletion allele was most likely to have originated from a Russian ancestor. In the Mexican kindred, the strikingly elevated LDL cholesterol level can be attributed to a homozygous frameshift LDLR variant p.E113fs.ConclusionsWhile the application of WES can provide a cost-effective way of identifying the genetic causes of FH, it often lacks sensitivity for detecting structural variants. Our finding of the LDLR exon 1 deletion highlights the broader utility of Linked-Read WGS in detecting SVs in the clinical setting, especially when HoFH patients remain undiagnosed after WES
Septic Arthritis and Multifocal Osteomyelitis Caused by Capnocytophaga Canimorsus: A Case Report
Capnocytophaga; Osteomyelitis; Septic arthritisCapnocitofaga; Osteomielitis; Artritis sépticaCapnocytophaga; Osteomielitis; Artritis sèpticaMicrobiological diagnosis of chronic osteoarticular infections remains a major challenge, particularly when the clinical presentation is atypical and the pathogen is uncommon. In this unique case, Capnocytophaga canimorsus, a microorganism belonging to the oral microbiota of some domestic animals, caused septic arthritis and multifocal osteomyelitis in the long bone of a 43-year-old immunocompetent man. The patient was treated with two-stage surgery and local and systemic antibiotic therapy, and had a successful recovery. C. canimorsus should be considered as a possible etiological agent in patients with osteoarticular pathology and a history of exposure to domestic animals
SMASH, a fragmentation and sequencing method for genomic copy number analysis
Copy number variants (CNVs) underlie a significant amount of genetic diversity and disease. CNVs can be detected by a
number of means, including chromosomal microarray analysis (CMA) and whole-genome sequencing (WGS), but these approaches
suffer from either limited resolution (CMA) or are highly expensive for routine screening (both CMA and WGS).
As an alternative, we have developed a next-generation sequencing-based method for CNV analysis termed SMASH, for
short multiply aggregated sequence homologies. SMASH utilizes random fragmentation of input genomic DNA to create
chimeric sequence reads, from which multiple mappable tags can be parsed using maximal almost-unique matches (MAMs).
The SMASH tags are then binned and segmented, generating a profile of genomic copy number at the desired resolution.
Because fewer reads are necessary relative to WGS to give accurate CNV data, SMASH libraries can be highly multiplexed,
allowing large numbers of individuals to be analyzed at low cost. Increased genomic resolution can be achieved by sequencing
to higher depth
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Aspirin-Trigge red-Resolvin D1 reduces mucosal inflammation and promotes resolution in a murine model of acute lung injury
Acute Lung Injury (ALI) is a severe illness with excess mortality and no specific therapy. Protective actions were recently uncovered for docosahexaenoic acid -derived mediators, including D-series resolvins. Here, we used a murine self-limited model of hydrochloric acid-induced ALI to determine the effects of aspirin-triggered resolvin D1 (AT-RvD1) on mucosal injury. RvD1 and its receptor ALX/FPR2 were identified in murine lung after ALI. AT-RvD1 (~0.5 – 5 μg/kg) decreased peak inflammation, including bronchoalveolar lavage fluid (BALF) neutrophils by ~75%. Animals treated with AT-RvD1 had improved epithelial and endothelial barrier integrity and decreased airway resistance concomitant with increased BALF epinephrine levels. AT-RvD1 inhibited neutrophil-platelet heterotypic interactions by down-regulating both P-selectin and its ligand CD24. AT-RvD1 also significantly decreased levels of BALF pro-inflammatory cytokines, including IL-1β, IL-6, KC and TNF-α, and decreased NF-κB phosphorylated p65 nuclear translocation. Together, these findings indicate that AT-RvD1 displays potent mucosal protection and promotes catabasis after ALI
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