Topography and instability of monolayers near domain boundaries

We theoretically study the topography of a biphasic surfactant monolayer in the vicinity of domain boundaries. The differing elastic properties of the two phases generally lead to a nonflat topography of ``mesas'', where domains of one phase are elevated with respect to the other phase. The mesas are steep but low, having heights of up to 10 nm. As the monolayer is laterally compressed, the mesas develop overhangs and eventually become unstable at a surface tension of about K(dc)^2 (dc being the difference in spontaneous curvature and K a bending modulus). In addition, the boundary is found to undergo a topography-induced rippling instability upon compression, if its line tension is smaller than about K(dc). The effect of diffuse boundaries on these features and the topographic behavior near a critical point are also examined. We discuss the relevance of our findings to several experimental observations related to surfactant monolayers: (i) small topographic features recently found near domain boundaries; (ii) folding behavior observed in mixed phospholipid monolayers and model lung surfactants; (iii) roughening of domain boundaries seen under lateral compression; (iv) the absence of biphasic structures in tensionless surfactant films.Comment: 17 pages, 9 figures, using RevTeX and epsf, submitted to Phys Rev

Years of life that could be saved from prevention of hepatocellular carcinoma

BACKGROUND: Hepatocellular carcinoma (HCC) causes premature death and loss of life expectancy worldwide. Its primary and secondary prevention can result in a significant number of years of life saved. AIM: To assess how many years of life are lost after HCC diagnosis. METHODS: Data from 5346 patients with first HCC diagnosis were used to estimate lifespan and number of years of life lost after tumour onset, using a semi-parametric extrapolation having as reference an age-, sex- and year-of-onset-matched population derived from national life tables. RESULTS: Between 1986 and 2014, HCC lead to an average of 11.5 years-of-life lost for each patient. The youngest age-quartile group (18-61 years) had the highest number of years-of-life lost, representing approximately 41% of the overall benefit obtainable from prevention. Advancements in HCC management have progressively reduced the number of years-of-life lost from 12.6 years in 1986-1999, to 10.7 in 2000-2006 and 7.4 years in 2007-2014. Currently, an HCC diagnosis when a single tumour <2 cm results in 3.7 years-of-life lost while the diagnosis when a single tumour 65 2 cm or 2/3 nodules still within the Milan criteria, results in 5.0 years-of-life lost, representing the loss of only approximately 5.5% and 7.2%, respectively, of the entire lifespan from birth. CONCLUSIONS: Hepatocellular carcinoma occurrence results in the loss of a considerable number of years-of-life, especially for younger patients. In recent years, the increased possibility of effectively treating this tumour has improved life expectancy, thus reducing years-of-life lost

Phospholipid Composition Modulates Carbon Nanodiamond-Induced Alterations in Phospholipid Domain Formation

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Langmuir, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/la504923j.The focus of this work is to elucidate how phospholipid composition can modulate lipid nanoparticle interactions in phospholipid monolayer systems. We report on alterations in lipid domain formation induced by anionically engineered carbon nanodiamonds (ECNs) as a function of lipid headgroup charge and alkyl chain saturation. Using surface pressure vs area isotherms, monolayer compressibility, and fluorescence microscopy, we found that anionic ECNs induced domain shape alterations in zwitterionic phosphatidylcholine lipids, irrespective of the lipid alkyl chain saturation, even when the surface pressure vs area isotherms did not show any significant changes. Bean-shaped structures characteristic of dipalmitoylphosphatidylcholine (DPPC) were converted to multilobed, fractal, or spiral domains as a result of exposure to ECNs, indicating that ECNs lower the line tension between domains in the case of zwitterionic lipids. For membrane systems containing anionic phospholipids, ECN-induced changes in domain packing were related to the electrostatic interactions between the anionic ECNs and the anionic lipid headgroups, even when zwitterionic lipids are present in excess. By comparing the measured size distributions with our recently developed theory derived by minimizing the free energy associated with the domain energy and mixing entropy, we found that the change in line tension induced by anionic ECNs is dominated by the charge in the condensed lipid domains. Atomic force microscopy images of the transferred anionic films confirm that the location of the anionic ECNs in the lipid monolayers is also modulated by the charge on the condensed lipid domains. Because biological membranes such as lung surfactants contain both saturated and unsaturated phospholipids with different lipid headgroup charges, our results suggest that when studying potential adverse effects of nanoparticles on biological systems the role of lipid compositions cannot be neglected

IL28B Genetic Variation Is Associated with Spontaneous Clearance of Hepatitis C Virus, Treatment Response, Serum IL-28B Levels in Chinese Population

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; The interleukin-28B gene (IL28B) locus has been associated with host resistance to hepatitis C virus (HCV) infection and response to PEG-IFN/RBV treatment in western populations. This study was to determine whether this gene variant is also associated with spontaneous clearance of HCV infection, treatment response and IL-28B protein production in Chinese patients.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; We genotyped IL28B genetic variations (rs12980275, rs8103142, rs8099917 and rs12979860) by pyrosequencing DNA samples from cohorts consisting of 529 subjects with persistent HCV infection, 196 subjects who cleared the infection, 171 healthy individuals and 235 chronic HCV patients underwent IFN/RBV treatment. The expression of IL-28B were measured by ELISA and RT-PCR.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; We found that the four IL28B variants were in complete linkage disequilibrium (r2 = 0.97–0.98). The rs12979860 CC genotype was strongly associated with spontaneously HCV clearance and successful IFN/RBV treatment compared to the CT/TT. IL-28B levels in persistent HCV patients were significantly lower than subjects who spontaneously resolved HCV and healthy controls and were also associated with high levels of ALT (alanine aminotransferase) and AST (aspartate aminotransferase). IL-28B levels were also significantly lower in individuals carrying T alleles than CC homozygous.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Thus, the rs12979860-CC variant upstream of IL28B gene is associated with spontaneous clearance of HCV, susceptible to IFN/RBV treatment and increased IL-28B levels in this Chinese population.&lt;/p&gt

HCV genome-wide genetic analyses in context of disease progression and hepatocellular carcinoma

<div><p>Hepatitis C virus (HCV) is a major cause of hepatitis and hepatocellular carcinoma (HCC) world-wide. Most HCV patients have relatively stable disease, but approximately 25% have progressive disease that often terminates in liver failure or HCC. HCV is highly variable genetically, with seven genotypes and multiple subtypes per genotype. This variation affects HCV’s sensitivity to antiviral therapy and has been implicated to contribute to differences in disease. We sequenced the complete viral coding capacity for 107 HCV genotype 1 isolates to determine whether genetic variation between independent HCV isolates is associated with the rate of disease progression or development of HCC. Consensus sequences were determined by sequencing RT-PCR products from serum or plasma. Positions of amino acid conservation, amino acid diversity patterns, selection pressures, and genome-wide patterns of amino acid covariance were assessed in context of the clinical phenotypes. A few positions were found where the amino acid distributions or degree of positive selection differed between in the HCC and cirrhotic sequences. All other assessments of viral genetic variation and HCC failed to yield significant associations. Sequences from patients with slow disease progression were under a greater degree of positive selection than sequences from rapid progressors, but all other analyses comparing HCV from rapid and slow disease progressors were statistically insignificant. The failure to observe distinct sequence differences associated with disease progression or HCC employing methods that previously revealed strong associations with the outcome of interferon α-based therapy implies that variable ability of HCV to modulate interferon responses is not a dominant cause for differential pathology among HCV patients. This lack of significant associations also implies that host and/or environmental factors are the major causes of differential disease presentation in HCV patients.</p></div