711 research outputs found
Hepatic progenitor cells from adult human livers for cell transplantation.
Objective: Liver regeneration is mainly based on cellular
self-renewal including progenitor cells. Efforts have been
made to harness this potential for cell transplantation, but
shortage of hepatocytes and premature differentiated
progenitor cells from extra-hepatic organs are limiting
factors. Histological studies implied that resident cells in
adult liver can proliferate, have bipotential character and
may be a suitable source for cell transplantation.
Methods: Particular cell populations were isolated after
adequate tissue dissociation. Single cell suspensions were
purified by Thy-1 positivity selection, characterised in vitro
and transplanted in immunodeficient Pfp/Rag2 mice.
Results: Thy-1+ cells that are mainly found in the portal
tract and the surrounding parenchyma, were isolated from
surgical liver tissue with high yields from specimens with
histological signs of regeneration. Thy-1+ cell populations
were positive for progenitor (CD34, c-kit, CK14, M2PK,
OV6), biliary (CK19) and hepatic (HepPar1) markers
revealing their progenitor as well as hepatic and biliary
nature. The potential of Thy-1+ cells for differentiation in
vitro was demonstrated by increased mRNA and protein
expression for hepatic (CK18, HepPar1) and biliary (CK7)
markers during culture while progenitor markers CK14,
chromogranin A and nestin were reduced. After
transplantation of Thy-1+ cells into livers of immunodeficient
mice, engraftment was predominantly seen in the
periportal portion of the liver lobule. Analysis of in situ
material revealed that transplanted cells express human
hepatic markers HepPar1 and albumin, indicating functional
engraftment.
Conclusion: Bipotential progenitor cells from human
adult livers can be isolated using Thy-1 and might be a
potential candidate for cell treatment in liver diseases
Geometric approach to nonvariational singular elliptic equations
In this work we develop a systematic geometric approach to study fully
nonlinear elliptic equations with singular absorption terms as well as their
related free boundary problems. The magnitude of the singularity is measured by
a negative parameter , for , which reflects on
lack of smoothness for an existing solution along the singular interface
between its positive and zero phases. We establish existence as well sharp
regularity properties of solutions. We further prove that minimal solutions are
non-degenerate and obtain fine geometric-measure properties of the free
boundary . In particular we show sharp
Hausdorff estimates which imply local finiteness of the perimeter of the region
and a.e. weak differentiability property of
.Comment: Paper from D. Araujo's Ph.D. thesis, distinguished at the 2013 Carlos
Gutierrez prize for best thesis, Archive for Rational Mechanics and Analysis
201
A genome-wide linkage and association scan reveals novel loci for autism
Member of the Autism Genome Project Consortium: Astrid M. VicenteAlthough autism is a highly heritable neurodevelopmental disorder, attempts to identify specific susceptibility genes have thus far met with limited success. Genome-wide association studies using half a million or more markers, particularly those with very large sample sizes achieved through meta-analysis, have shown great success in mapping genes for other complex genetic traits. Consequently, we initiated a linkage and association mapping study using half a million genome-wide single nucleotide polymorphisms (SNPs) in a common set of 1,031 multiplex autism families (1,553 affected offspring). We identified regions of suggestive and significant linkage on chromosomes 6q27 and 20p13, respectively. Initial analysis did not yield genome-wide significant associations; however, genotyping of top hits in additional families revealed an SNP on chromosome 5p15 (between SEMA5A and TAS2R1) that was significantly associated with autism (P = 2 x 10(-7)). We also demonstrated that expression of SEMA5A is reduced in brains from autistic patients, further implicating SEMA5A as an autism susceptibility gene. The linkage regions reported here provide targets for rare variation screening whereas the discovery of a single novel association demonstrates the action of common variants
Transport Properties of the Diluted Lorentz Slab
We study the behavior of a point particle incident from the left on a slab of
a randomly diluted triangular array of circular scatterers. Various scattering
properties, such as the reflection and transmission probabilities and the
scattering time are studied as a function of thickness and dilution. We show
that a diffusion model satisfactorily describes the mentioned scattering
properties. We also show how some of these quantities can be evaluated exactly
and their agreement with numerical experiments. Our results exhibit the
dependence of these scattering data on the mean free path. This dependence
again shows excellent agreement with the predictions of a Brownian motion
model.Comment: 14 pages of text in LaTeX, 7 figures in Postscrip
Nonclassical phase-space trajectories for the damped harmonic quantum oscillator
The phase-space path-integral approach to the damped harmonic oscillator is
analyzed beyond the Markovian approximation. It is found that pairs of
nonclassical trajectories contribute to the path-integral representation of the
Wigner propagating function. Due to the linearity of the problem, the sum
coordinate of a pair still satisfies the classical equation of motion.
Furthermore, it is shown that the broadening of the Wigner propagating function
of the damped oscillator arises due to the time-nonlocal interaction mediated
by the heat bath.Comment: 8 pages, 3 figures, accepted for publication in Chemical Physic
Tunable Lyapunov exponent in inverse magnetic billiards
The stability properties of the classical trajectories of charged particles
are investigated in a two dimensional stadium-shaped inverse magnetic domain,
where the magnetic field is zero inside the stadium domain and constant
outside. In the case of infinite magnetic field the dynamics of the system is
the same as in the Bunimovich billiard, i.e., ergodic and mixing. However, for
weaker magnetic fields the phase space becomes mixed and the chaotic part
gradually shrinks. The numerical measurements of the Lyapunov exponent
(performed with a novel method) and the integrable/chaotic phase space volume
ratio show that both quantities can be smoothly tuned by varying the external
magnetic field. A possible experimental realization of the arrangement is also
discussed.Comment: 4 pages, 6 figure
Slow fluctuations in enhanced Raman scattering and surface roughness relaxation
We propose an explanation for the recently measured slow fluctuations and
``blinking'' in the surface enhanced Raman scattering (SERS) spectrum of single
molecules adsorbed on a silver colloidal particle. We suggest that these
fluctuations may be related to the dynamic relaxation of the surface roughness
on the nanometer scale and show that there are two classes of roughness with
qualitatively different dynamics. The predictions agree with measurements of
surface roughness relaxation. Using a theoretical model for the kinetics of
surface roughness relaxation in the presence of charges and optical electrical
fields, we predict that the high-frequency electromagnetic field increases both
the effective surface tension and the surface diffusion constant and thus
accelerates the surface smoothing kinetics and time scale of the Raman
fluctuations in manner that is linear with the laser power intensity, while the
addition of salt retards the surface relaxation kinetics and increases the time
scale of the fluctuations. These predictions are in qualitative agreement with
the Raman experiments
Non-linear regression models for Approximate Bayesian Computation
Approximate Bayesian inference on the basis of summary statistics is
well-suited to complex problems for which the likelihood is either
mathematically or computationally intractable. However the methods that use
rejection suffer from the curse of dimensionality when the number of summary
statistics is increased. Here we propose a machine-learning approach to the
estimation of the posterior density by introducing two innovations. The new
method fits a nonlinear conditional heteroscedastic regression of the parameter
on the summary statistics, and then adaptively improves estimation using
importance sampling. The new algorithm is compared to the state-of-the-art
approximate Bayesian methods, and achieves considerable reduction of the
computational burden in two examples of inference in statistical genetics and
in a queueing model.Comment: 4 figures; version 3 minor changes; to appear in Statistics and
Computin
No Association Between Screening for Hepatocellular Carcinoma and Reduced Cancer-Related Mortality in Patients With Cirrhosis
Background & Aims: Screening patients with cirrhosis for hepatocellular carcinoma (HCC) has been recommended. We conducted a matched case–control study within the US Veterans Affairs (VA) health care system to determine whether screening by abdominal ultrasonography (USS) and/or by measuring serum level of α-fetoprotein (AFP) was associated with decreased cancer-related mortality in patients with cirrhosis. Methods: We defined cases (n = 238) as patients with cirrhosis who died of HCC from January 1, 2013 through August 31, 2015 and had been in VA care with a diagnosis of cirrhosis for at least 4 years before the diagnosis of HCC. We matched each case to 1 control (n = 238), defined as a patient with cirrhosis who did not die of HCC and had been in VA care for at least 4 years before the date of the matched case's HCC diagnosis. Controls were matched to cases by year of cirrhosis diagnosis, race and ethnicity, age, sex, etiology of cirrhosis, Model for End-Stage Liver Disease score, and VA medical center. We identified all USS and serum AFP tests performed within 4 years before the date of HCC diagnosis in cases or the equivalent index date in controls and determined by chart extraction (blinded to case or control status) whether these tests were performed for screening. Results: There were no significant differences between cases and controls in the proportions of patients who underwent screening USS (52.9% vs 54.2%), screening measurement of serum AFP (74.8% vs 73.5%), screening USS or measurement of serum AFP (81.1% vs 79.4%), or screening USS and measurement of serum AFP (46.6% vs 48.3%) within 4 years before the index date, with or without adjusting for potential confounders. There also was no difference in receipt of these screening tests within 1, 2, or 3 years before the index date. Conclusions: In a matched case–control study of the VA health care system, we found that screening patients with cirrhosis for HCC by USS, measurement of serum AFP, either test, or both tests was not associated with decreased HCC-related mortality. We encourage additional case–control studies to evaluate the efficacy of screening for HCC in other health care systems, in which available records are sufficiently detailed to enable identification of the indication for USS and AFP tests
Reply
Reply. We are grateful for the interest others have shown in our paper, which allowed us to clarify critical aspects of the case-control study design and the nature of our study population
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