On the stability of the exact solutions of the dual-phase lagging model of heat conduction

The dual-phase lagging (DPL) model has been considered as one of the most promising theoretical approaches to generalize the classical Fourier law for heat conduction involving short time and space scales. Its applicability, potential, equivalences, and possible drawbacks have been discussed in the current literature. In this study, the implications of solving the exact DPL model of heat conduction in a three-dimensional bounded domain solution are explored. Based on the principle of causality, it is shown that the temperature gradient must be always the cause and the heat flux must be the effect in the process of heat transfer under the dual-phase model. This fact establishes explicitly that the single- and DPL models with different physical origins are mathematically equivalent. In addition, taking into account the properties of the Lambert W function and by requiring that the temperature remains stable, in such a way that it does not go to infinity when the time increases, it is shown that the DPL model in its exact form cannot provide a general description of the heat conduction phenomena

The Evolution of the Major Hepatitis C Genotypes Correlates with Clinical Response to Interferon Therapy

Patients chronically infected with hepatitis C virus (HCV) require significantly different durations of therapy and achieve substantially different sustained virologic response rates to interferon-based therapies, depending on the HCV genotype with which they are infected. There currently exists no systematic framework that explains these genotype-specific response rates. Since humans are the only known natural hosts for HCV-a virus that is at least hundreds of years old-one possibility is that over the time frame of this relationship, HCV accumulated adaptive mutations that confer increasing resistance to the human immune system. Given that interferon therapy functions by triggering an immune response, we hypothesized that clinical response rates are a reflection of viral evolutionary adaptations to the immune system.We have performed the first phylogenetic analysis to include all available full-length HCV genomic sequences (n = 345). This resulted in a new cladogram of HCV. This tree establishes for the first time the relative evolutionary ages of the major HCV genotypes. The outcome data from prospective clinical trials that studied interferon and ribavirin therapy was then mapped onto this new tree. This mapping revealed a correlation between genotype-specific responses to therapy and respective genotype age. This correlation allows us to predict that genotypes 5 and 6, for which there currently are no published prospective trials, will likely have intermediate response rates, similar to genotype 3. Ancestral protein sequence reconstruction was also performed, which identified the HCV proteins E2 and NS5A as potential determinants of genotype-specific clinical outcome. Biochemical studies have independently identified these same two proteins as having genotype-specific abilities to inhibit the innate immune factor double-stranded RNA-dependent protein kinase (PKR).An evolutionary analysis of all available HCV genomes supports the hypothesis that immune selection was a significant driving force in the divergence of the major HCV genotypes and that viral factors that acquired the ability to inhibit the immune response may play a role in determining genotype-specific response rates to interferon therapy