191 research outputs found
Advanced imaging and tissue engineering of the human limbal epithelial stem cell niche
The limbal epithelial stem cell niche provides a unique, physically protective environment in which limbal epithelial stem cells reside in close proximity with accessory cell types and their secreted factors. The use of advanced imaging techniques is described to visualize the niche in three dimensions in native human corneal tissue. In addition, a protocol is provided for the isolation and culture of three different cell types, including human limbal epithelial stem cells from the limbal niche of human donor tissue. Finally, the process of incorporating these cells within plastic compressed collagen constructs to form a tissue-engineered corneal limbus is described and how immunohistochemical techniques may be applied to characterize cell phenotype therein
Large Scale Structure of the Universe
Galaxies are not uniformly distributed in space. On large scales the Universe
displays coherent structure, with galaxies residing in groups and clusters on
scales of ~1-3 Mpc/h, which lie at the intersections of long filaments of
galaxies that are >10 Mpc/h in length. Vast regions of relatively empty space,
known as voids, contain very few galaxies and span the volume in between these
structures. This observed large scale structure depends both on cosmological
parameters and on the formation and evolution of galaxies. Using the two-point
correlation function, one can trace the dependence of large scale structure on
galaxy properties such as luminosity, color, stellar mass, and track its
evolution with redshift. Comparison of the observed galaxy clustering
signatures with dark matter simulations allows one to model and understand the
clustering of galaxies and their formation and evolution within their parent
dark matter halos. Clustering measurements can determine the parent dark matter
halo mass of a given galaxy population, connect observed galaxy populations at
different epochs, and constrain cosmological parameters and galaxy evolution
models. This chapter describes the methods used to measure the two-point
correlation function in both redshift and real space, presents the current
results of how the clustering amplitude depends on various galaxy properties,
and discusses quantitative measurements of the structures of voids and
filaments. The interpretation of these results with current theoretical models
is also presented.Comment: Invited contribution to be published in Vol. 8 of book "Planets,
Stars, and Stellar Systems", Springer, series editor T. D. Oswalt, volume
editor W. C. Keel, v2 includes additional references, updated to match
published versio
Effect of Cryogrinding on Chemical Stability of the Sparingly Water-Soluble Drug Furosemide
Purpose To investigate the effect of cryogrinding on chemical
stability of the diuretic agent furosemide and its mixtures with
selected excipients.
Methods Furosemide was ground at liquid nitrogen temperature
for 30, 60, 120 and 180 min. Mixtures of furosemide-PVP
and furosemide-inulin (1:1) were milled under cryogenic conditions.
Materials were analyzed by XRD, UPLC, MS and NMR.
Results Upon increasing the milling time, a significant build-up
of an unidentified impurity 1, probably the main degradation
product, was noticed. Cogrinding of furosemide with PVP and
inulin worsened chemical stabilization of the pharmaceutical.
The main degradation product formed upon cryomilling was
subsequently identified as 4-chloro-5-sulfamoylanthranilic acid
(CSA). Based on some theoretical considerations involving
specific milling conditions, the milling intensity and an expected
specific milling dose have been calculated. Results indicate that
cryogenic grinding is capable to initiate mechanically induced
decomposition of furosemide.Conclusions Cryogenic grinding can activate and accelerate
not only structural changes (solid state amorphization) but also
chemical decomposition of pharmaceuticals. A cryogenic
milling device should be considered as a chemical reactor,
where under favourable conditions chemical reactions could be
mechanically initiated
Revised cutoff values of ALT and HBV DNA level can better differentiate HBeAg (-) chronic inactive HBV patients from active carriers
<p>Abstract</p> <p>Background and Aims</p> <p>ELISA is still used as primary test for diagnosis HBV disease. However, ELISA-positive patients were marked as HBV inactive after confirmation with PCR and vice versa. Our aim was to assess the performance of new cut-off value of ALT, HBV DNA load and significance of AST as screening tool for HBeAg (-) chronic active or inactive patients in Pakistani population.</p> <p>Materials and methods</p> <p>In a cross-sectional, cohort study, 567 HBeAg (-) patients followed for one year were selected. Patients with persistent elevated ALT than normal and HBV DNA ≥ 100,000 copies/mL were taken as active chronic. Diagnostic values for ALT, AST and HBV DNA load in HBV HBeAg (-) chronic active and inactive patients compared using receiver operation characteristic (ROC) curves.</p> <p>Results</p> <p>Of 567 HBeAg (-) patients, 228 were classified as chronic inactive and 339 as active. HBV infection was dominant in male. Serum ALT, AST and HBV DNA levels showed significant and high AUROC to differentiate chronic HBeAg (-) inactive patients from active. AUROC for Serum ALT, AST and HBV DNA were observed 0.997, 0.969 and 1.000, respectively. For revised cut off value for ALT (30 IU/L for male and 19 IU/L for female) and HBV DNA load ≥100,000 copies/mL, a PPV of 97%, NPV of 94%, a sensitivity of 98%, and a specificity of 92% was observed to discriminate active carriers from inactive carriers. We also observed 93.5% specificity, 83.1% sensitivity, 82% PPV and 89.5% NPV for AST ≤20 IU/L to differentiate inactive carriers from active ones in our study group.</p> <p>Conclusions</p> <p>Revised cut off value of ALT and NIH derived HBV DNA value can better discriminate between HBeAg (-) chronic active and inactive patients.</p
Understanding Galaxy Formation and Evolution
The old dream of integrating into one the study of micro and macrocosmos is
now a reality. Cosmology, astrophysics, and particle physics intersect in a
scenario (but still not a theory) of cosmic structure formation and evolution
called Lambda Cold Dark Matter (LCDM) model. This scenario emerged mainly to
explain the origin of galaxies. In these lecture notes, I first present a
review of the main galaxy properties, highlighting the questions that any
theory of galaxy formation should explain. Then, the cosmological framework and
the main aspects of primordial perturbation generation and evolution are
pedagogically detached. Next, I focus on the ``dark side'' of galaxy formation,
presenting a review on LCDM halo assembling and properties, and on the main
candidates for non-baryonic dark matter. It is shown how the nature of
elemental particles can influence on the features of galaxies and their
systems. Finally, the complex processes of baryon dissipation inside the
non-linearly evolving CDM halos, formation of disks and spheroids, and
transformation of gas into stars are briefly described, remarking on the
possibility of a few driving factors and parameters able to explain the main
body of galaxy properties. A summary and a discussion of some of the issues and
open problems of the LCDM paradigm are given in the final part of these notes.Comment: 50 pages, 10 low-resolution figures (for normal-resolution, DOWNLOAD
THE PAPER (PDF, 1.9 Mb) FROM http://www.astroscu.unam.mx/~avila/avila.pdf).
Lectures given at the IV Mexican School of Astrophysics, July 18-25, 2005
(submitted to the Editors on March 15, 2006
Formation of Supermassive Black Holes
Evidence shows that massive black holes reside in most local galaxies.
Studies have also established a number of relations between the MBH mass and
properties of the host galaxy such as bulge mass and velocity dispersion. These
results suggest that central MBHs, while much less massive than the host (~
0.1%), are linked to the evolution of galactic structure. In hierarchical
cosmologies, a single big galaxy today can be traced back to the stage when it
was split up in hundreds of smaller components. Did MBH seeds form with the
same efficiency in small proto-galaxies, or did their formation had to await
the buildup of substantial galaxies with deeper potential wells? I briefly
review here some of the physical processes that are conducive to the evolution
of the massive black hole population. I will discuss black hole formation
processes for `seed' black holes that are likely to place at early cosmic
epochs, and possible observational tests of these scenarios.Comment: To appear in The Astronomy and Astrophysics Review. The final
publication is available at http://www.springerlink.co
Small but crucial : the novel small heat shock protein Hsp21 mediates stress adaptation and virulence in Candida albicans
Peer reviewedPublisher PD
Deficiency of Thioredoxin Binding Protein-2 (TBP-2) Enhances TGF-β Signaling and Promotes Epithelial to Mesenchymal Transition
Transforming growth factor beta (TGF-β) has critical roles in regulating cell growth, differentiation, apoptosis, invasion and epithelial-mesenchymal transition (EMT) of various cancer cells. TGF-β-induced EMT is an important step during carcinoma progression to invasion state. Thioredoxin binding protein-2 (TBP-2, also called Txnip or VDUP1) is downregulated in various types of human cancer, and its deficiency results in the earlier onset of cancer. However, it remains unclear how TBP-2 suppresses the invasion and metastasis of cancer.In this study, we demonstrated that TBP-2 deficiency increases the transcriptional activity in response to TGF-β and also enhances TGF-β-induced Smad2 phosphorylation levels. Knockdown of TBP-2 augmented the TGF-β-responsive expression of Snail and Slug, transcriptional factors related to TGF-β-mediated induction of EMT, and promoted TGF-β-induced spindle-like morphology consistent with the depletion of E-Cadherin in A549 cells.Our results indicate that TBP-2 deficiency enhances TGF-β signaling and promotes TGF-β-induced EMT. The control of TGF-β-induced EMT is critical for the inhibition of the invasion and metastasis. Thus TBP-2, as a novel regulatory molecule of TGF-β signaling, is likely to be a prognostic indicator or a potential therapeutic target for preventing tumor progression
Bayesian analysis of cosmic structures
We revise the Bayesian inference steps required to analyse the cosmological
large-scale structure. Here we make special emphasis in the complications which
arise due to the non-Gaussian character of the galaxy and matter distribution.
In particular we investigate the advantages and limitations of the
Poisson-lognormal model and discuss how to extend this work. With the lognormal
prior using the Hamiltonian sampling technique and on scales of about 4 h^{-1}
Mpc we find that the over-dense regions are excellent reconstructed, however,
under-dense regions (void statistics) are quantitatively poorly recovered.
Contrary to the maximum a posteriori (MAP) solution which was shown to
over-estimate the density in the under-dense regions we obtain lower densities
than in N-body simulations. This is due to the fact that the MAP solution is
conservative whereas the full posterior yields samples which are consistent
with the prior statistics. The lognormal prior is not able to capture the full
non-linear regime at scales below ~ 10 h^{-1} Mpc for which higher order
correlations would be required to describe the matter statistics. However, we
confirm as it was recently shown in the context of Ly-alpha forest tomography
that the Poisson-lognormal model provides the correct two-point statistics (or
power-spectrum).Comment: 11 pages, 1 figure, report for the Astrostatistics and Data Mining
workshop, La Palma, Spain, 30 May - 3 June 2011, to appear in Springer Series
on Astrostatistic
Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015
SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation
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