2,355 research outputs found
Electrospun organicâinorganic nanohybrids as sustained release drug delivery systems
In this work, the non-steroidal anti-inflammatory drugs ibuprofen (ibu) and ketoprofen (ket), both poorly soluble in water, were first intercalated into layered double hydroxide (LDH) nanoparticles. The drugâLDH composites were then mixed with poly(Îľ-caprolactone) (PCL) at 5% and 10% w/w ratios and processed into fibers via electrospinning, yielding organicâinorganic nanohybrids. PCL/drug fibers were additionally prepared as controls. The average diameter of the fibers ranged from 400 to 1000 nm. The fibers are found to be smooth and cylindrical, with the LDH-containing systems having more homogenous fibers than those without the inorganic filler. From in vitro drug release tests, it was determined that more than 90% of the intercalated ibu and ket were released from the drugâLDH nanohybrids within the first 4 hours. Similarly, more than 60% of the incorporated drug was freed from the PCL/drug fibers in this time period. However, the release rates of both ibu and ket from the drugâLDH loaded PCL fibers were significantly slower. Only 44â48% of ibu was released from the PCL/ibuâLDH system after 5 days, while the amount released in the case of ket was 20â25%. In addition, drug release was still ongoing after 5 days for all the PCL/drugâLDH samples. These systems are thus proposed to have potential as implantable drug delivery systems
Avalanche precursors of failure in hierarchical fuse networks
We study precursors of failure in hierarchical random fuse network models
which can be considered as idealizations of hierarchical (bio)materials where
fibrous assemblies are held together by multi-level (hierarchical) cross-links.
When such structures are loaded towards failure, the patterns of precursory
avalanche activity exhibit generic scale invariance: Irrespective of load,
precursor activity is characterized by power-law avalanche size distributions
without apparent cut-off, with power-law exponents that decrease continuously
with increasing load. This failure behavior and the ensuing super-rough crack
morphology differ significantly from the findings in non-hierarchical
structures
BRCA1 function in T lymphocytes: a cellular specificity of a different kind
Recent work by Mak et al demonstrates that mice carrying a T-cell-specific disruption of the brca1 gene display markedly impaired T-lymphocyte development and proliferation in the absence of any increased tendency for the formation of tumors. Interestingly, the extent of these defects was found to be highly dependent on cellular context. Contrasting the rather broad tissue expression pattern of brca1 against its exquisitely selective etiologic role in cancers of the breast and ovary, many of us are left to ponder - where is the specificity
Moduli Stabilization and Inflationary Cosmology with Poly-Instantons in Type IIB Orientifolds
Equipped with concrete examples of Type IIB orientifolds featuring
poly-instanton corrections to the superpotential, the effects on moduli
stabilization and inflationary cosmology are analyzed. Working in the framework
of the LARGE volume scenario, the Kaehler modulus related to the size of the
four-cycle supporting the poly-instanton contributes sub-dominantly to the
scalar potential. It is shown that this Kaehler modulus gets stabilized and, by
displacing it from its minimum, can play the role of an inflaton. Subsequent
cosmological implications are discussed and compared to experimental data.Comment: 38 pages, 7 figures, Reference added, Typo fixed, Published versio
From Nonspecific DNAâProtein Encounter Complexes to the Prediction of DNAâProtein Interactions
Š2009 Gao, Skolnick. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.doi:10.1371/journal.pcbi.1000341DNAâprotein interactions are involved in many essential biological activities. Because there is no simple mapping code between DNA base pairs and protein amino acids, the prediction of DNAâprotein interactions is a challenging problem. Here, we present a novel computational approach for predicting DNA-binding protein residues and DNAâprotein interaction modes without knowing its specific DNA target sequence. Given the structure of a DNA-binding protein, the method first generates an ensemble of complex structures obtained by rigid-body docking with a nonspecific canonical B-DNA. Representative models are subsequently selected through clustering and ranking by their DNAâprotein interfacial energy. Analysis of these encounter complex models suggests that the recognition sites for specific DNA binding are usually favorable interaction sites for the nonspecific DNA probe and that nonspecific DNAâprotein interaction modes exhibit some similarity to specific DNAâprotein binding modes. Although the method requires as input the knowledge that the protein binds DNA, in benchmark tests, it achieves better performance in identifying DNA-binding sites than three previously established methods, which are based on sophisticated machine-learning techniques. We further apply our method to protein structures predicted through modeling and demonstrate that our method performs satisfactorily on protein models whose root-mean-square Ca deviation from native is up to 5 Ă
from their native structures. This study provides valuable structural insights into how a specific DNA-binding protein interacts with a nonspecific DNA sequence. The similarity between the specific DNAâprotein interaction mode and nonspecific interaction modes may reflect an important sampling step in search of its specific DNA targets by a DNA-binding protein
Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in acute lung injury to reduce pulmonary dysfunction (HARP-2) trial : study protocol for a randomized controlled trial
Acute lung injury (ALI) is a common devastating clinical syndrome characterized by life-threatening respiratory failure requiring mechanical ventilation and multiple organ failure. There are in vitro, animal studies and pre-clinical data suggesting that statins may be beneficial in ALI. The Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in Acute lung injury to Reduce Pulmonary dysfunction (HARP-2) trial is a multicenter, prospective, randomized, allocation concealed, double-blind, placebo-controlled clinical trial which aims to test the hypothesis that treatment with simvastatin will improve clinical outcomes in patients with ALI
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