Effective algorithm of analysis of integrability via the Ziglin's method

In this paper we continue the description of the possibilities to use numerical simulations for mathematically rigorous computer assisted analysis of integrability of dynamical systems. We sketch some of the algebraic methods of studying the integrability and present a constructive algorithm issued from the Ziglin's approach. We provide some examples of successful applications of the constructed algorithm to physical systems.Comment: a figure added, version accepted to JDC

Viral dynamics during structured treatment interruptions of chronic human immunodeficiency virus type 1 infection

Although antiviral agents which block human immunodeficiency virus (HIV) replication can result in long-term suppression of viral loads to undetectable levels in plasma, long-term therapy fails to eradicate virus, which generally rebounds after a single treatment interruption. Multiple structured treatment interruptions (STIs) have been suggested as a possible strategy that may boost HIV-specific immune responses and control viral replication. We analyze viral dynamics during four consecutive STI cycles in 12 chronically infected patients with a history (>2 years) of viral suppression under highly active antiretroviral therapy. We fitted a simple model of viral rebound to the viral load data from each patient by using a novel statistical approach that allows us to overcome problems of estimating viral dynamics parameters when there are many viral load measurements below the limit of detection. There is an approximate halving of the average viral growth rate between the first and fourth STI cycles, yet the average time between treatment interruption and detection of viral loads in the plasma is approximately the same in the first and fourth interruptions. We hypothesize that reseeding of viral reservoirs during treatment interruptions can account for this discrepancy, although factors such as stochastic effects and the strength of HIV-specific immune responses may also affect the time to viral rebound. We also demonstrate spontaneous drops in viral load in later STIs, which reflect fluctuations in the rates of viral production and/or clearance that may be caused by a complex interaction between virus and target cells and/or immune responses

Phenotypic hypersusceptibility to multiple protease inhibitors and low replicative capacity in patients who are chronically infected with human immunodeficiency virus type 1

Increased susceptibility to the protease inhibitors saquinavir and amprenavir has been observed in human immunodeficiency virus type 1 (HIV-1) with specific mutations in protease (V82T and N88S). Increased susceptibility to ritonavir has also been described in some viruses from antiretroviral agent-naïve patients with primary HIV-1 infection in association with combinations of amino acid changes at polymorphic sites in the protease. Many of the viruses displaying increased susceptibility to protease inhibitors also had low replication capacity. In this retrospective study, we analyze the drug susceptibility phenotype and the replication capacity of virus isolates obtained at the peaks of viremia during five consecutive structured treatment interruptions in 12 chronically HIV-1-infected patients. Ten out of 12 patients had at least one sample with protease inhibitor hypersusceptibility (change ≤0.4-fold) to one or more protease inhibitor. Hypersusceptibility to different protease inhibitors was observed at variable frequency, ranging from 38% to amprenavir to 11% to nelfinavir. Pairwise comparisons between susceptibilities for the protease inhibitors showed a consistent correlation among all pairs. There was also a significant relationship between susceptibility to protease inhibitors and replication capacity in all patients. Replication capacity remained stable over the course of repetitive cycles of structured treatment interruptions. We could find no association between in vitro replication capacity and in vivo plasma viral load doubling time and CD4(+) and CD8(+) T-cell counts at each treatment interruption. Several mutations were associated with hypersusceptibility to each protease inhibitor in a univariate analysis. This study extends the association between hypersusceptibility to protease inhibitors and low replication capacity to virus isolated from chronically infected patients and highlights the complexity of determining the genetic basis of this phenomenon. The potential clinical relevance of protease inhibitor hypersusceptibility and low replication capacity to virologic response to protease inhibitor-based therapies deserves to be investigated further

Estimation procedure of the descriptor LAeq,T from the stabilization time of the sound pressure level value

Temporal structure of sound pressure level is a key aspect at the time of characterizing urban sound environments. In urban agglomerations, environmental noise levels fluctuate over a large range as a result of the great complexity of these settings, with considerable temporal and spatial heterogeneity. Furthermore, the domain in urban environments of noise sources, such as road traffic, commercial or leisure activities, construction works, etc., together with the occurrence of sudden sound-level maxima events (bells, sirens, vehicles at high traffic speed, honking horns...), which are quite frequent in urban agglomerations, generate the appearance of very high values of the impulsiveness of sound pressure level. This aspect causes a great influence on the time necessary for environmental noise levels to become stabilized, which is a key aspect for the accurate measurement, interpretation and guarantee of a statistically representative sample of a given urban sound environment. Therefore, the goal pursued in this work is to put forth a procedure for the calculation of a value of LAeq,T, representative of a certain urban location in a short-term time period, from the utilization of the value of the stabilization time of the sound pressure level

Rapid detection of free and bound toxins using molecularly imprinted silica/graphene oxide hybrids dagger

Rapid, selective detection of biological analytes is necessary for early diagnosis, but is often complicated by the analytes being bound to proteins and the lack of fast and reliable systems available for their direct assessment. Here, a cheap, easily-assembled molecularly imprinted silica/graphene oxide hybrid is developed, which can selectively detect toxins linked to early-stage chronic kidney disease, down to femtomolar concentrations within 5 minutes. The hybrid material is capable of simultaneously and separately measuring free and bound analytes using with an ultra-low limit of detection in the femtomolar range, and uses processes intrinsically adaptable to any charged molecular analy

Toughening by nanostructure

Block copolymer modified epoxy resins have generated significant interest since it was demonstrated that the combination could lead to nanostructured thermosets through self-assembly. Over moderate to high polymer concentration the system behaves as expected for a block copolymer in a solvent selective for one block. Two types of copolymers have been studied: non-reactive and reactive modifiers. Morphologies such as copolymer vesicle and spherical/wormlike micelles can be formed under the appropriate conditions. The enhancement of the modified thermosets' mechanical properties depends on the morphology adopted by the polymers. Besides improving mechanical properties, the morphology was found to also have an effect on the glass transition in the studied systems. In this review we collect the available data on the block copolymers used to fabricate nanostructured epoxy resins and critically appraise the properties reported