Mechanism for giant enhancement of transport induced by active fluctuations.

Understanding the role of active fluctuations in physics is a problem in statu nascendi appearing both as a hot topic and a major challenge. The reason for this is the fact that they are inherently nonequilibrium. This feature opens a landscape of phenomena yet to be explored that are absent in the presence of thermal fluctuations alone. Recently a paradoxical effect has been briefly communicated in which a free-particle transport induced by active fluctuations in the form white Poisson shot noise can be enormously boosted when the particle is additionally subjected to a periodic potential. In this work we considerably extend the original predictions and investigate the impact of statistics of active noise on the occurrence of this effect. We construct a toy model of the jump-relaxation process that allow us to identify different regimes of the free-particle transport boost and explain their corresponding mechanisms. Moreover, we formulate and interpret the conditions for statistics of active fluctuations that are necessary for the emergence of giant enhancement of the free-particle transport induced by the periodic potential. Our results are relevant not only for microscopic physical systems but also for biological ones such as, e.g., living cells where fluctuations generated by metabolic activities are active by default.

Periodic potential can enormously boost free-particle transport induced by active fluctuations.

Active fluctuations are detected in a growing number of systems due to self-propulsion mechanisms or collisions with an active environment. They drive the system far from equilibrium and can induce phenomena that are forbidden at equilibrium states by, e.g., fluctuation-dissipation relations and detailed balance symmetry. Understanding their role in living matter is emerging as a challenge for physics. Here we demonstrate a paradoxical effect in which a free-particle transport induced by active fluctuations can be boosted by many orders of magnitude when the particle is additionally subjected to a periodic potential. In contrast, within the realm of only thermal fluctuations, the velocity of a free particle exposed to a bias is reduced when the periodic potential is switched on. The presented mechanism is significant for understanding nonequilibrium environments such as living cells, where it can explain from a fundamental point of view why spatially periodic structures known as microtubules are necessary to generate impressively effective intracellular transport. Our findings can be readily corroborated experimentally, e.g., in a setup comprising a colloidal particle in an optically generated periodic potential.

Colossal Brownian yet non-Gaussian diffusion in a periodic potential: Impact of nonequilibrium noise amplitude statistics.

Last year, Bialas et al. [Phys. Rev. E 102, 042121 (2020)] studied an overdamped dynamics of nonequilibrium noise driven Brownian particle dwelling in a spatially periodic potential and discovered a novel class of Brownian, yet non-Gaussian diffusion. The mean square displacement of the particle grows linearly with time and the probability density for the particle position is Gaussian; however, the corresponding distribution for the increments is non-Gaussian. The latter property induces the colossal enhancement of diffusion, significantly exceeding the well known effect of giant diffusion. Here, we considerably extend the above predictions by investigating the influence of nonequilibrium noise amplitude statistics on the colossal Brownian, yet non-Gaussian diffusion. The tail of amplitude distribution crucially impacts both the magnitude of diffusion amplification and the Gaussianity of the position and increments statistics. Our results carry profound consequences for diffusive behavior in nonequilibrium settings such as living cells in which diffusion is a central transport mechanism.

Colossal Brownian yet non-Gaussian diffusion induced by nonequilibrium noise.

We report on Brownian, yet non-Gaussian diffusion, in which the mean square displacement of the particle grows linearly with time, and the probability density for the particle spreading is Gaussian like, but the probability density for its position increments possesses an exponentially decaying tail. In contrast to recent works in this area, this behavior is not a consequence of either a space- or time-dependent diffusivity, but is induced by external nonthermal noise acting on the particle dwelling in a periodic potential. The existence of the exponential tail in the increment statistics leads to colossal enhancement of diffusion, drastically surpassing the previously researched situation known as "giant" diffusion. This colossal diffusion enhancement crucially impacts a broad spectrum of the first arrival problems, such as diffusion limited reactions governing transport in living cells.

Identification of mutations in the HVR1 and PKR-BD regions in HCV-infected patients resistant to PEG-IFNα/RBV therapy.

The identification of mutations in the HVR1 region of hepatitis type C virus (HCV) is time-consuming and expensive, and there is a need for a rapid, inexpensive method of screening for these mutations to predict the ineffectiveness of pegylated interferon alpha combined with ribavirin (PEG-IFNα/RBV) therapy. The project was designed to evaluate the usefulness of the high resolution melting (HRM) technique to screen for mutation in the cDNAs encoding the HVR1 and protein kinase R-binding domain (PKR-BD) regions in a group of 36 patients infected with HCV and resistant to 12 months of combined therapy with PEG-IFNα/RBV. Viral RNA was isolated, reverse transcribed, and the fragments encoding the HVR1 and PKR-BD regions were polymerase chain reaction (PCR)-amplified, cloned, sequenced, and the melting profiles and the melting temperature (Tm) were determined by the HRM technique. After the treatment, the melting profiles of HVR1 cDNAs revealed a dominant peak corresponding to the Tm of about 85 °C (HCVs85) in almost all patients. One or more minor peaks were also observed, indicating the existence of cDNA(s) of different Tm. The HMR analysis suggested four typical forms of response to treatment. These suppositions were supported by sequencing. The HRM analysis revealed no changes in the melting profiles of PKR-BD cDNAs in the same patient before and after the therapy, suggesting that, within 12 months of treatment, new mutations were not introduced in PKR-BD. These findings were substantiated by sequencing. The HRM technique can be applied for the rapid screening for mutations in the cDNAs encoding the HVR and PKR-BD regions of HCV. We suggest that the detection of HCVs85 peak before the IFNα/RBV therapy might predict the ineffectiveness of treatment.

Application of a high-resolution melting technique for the rapid detection of partial replacement of HCV-1b by HCV-1a after PEG-IFNα/RBV therapy.

A modified method which can be used for the rapid screening of mutations in the protein kinase R-binding domain (PKR-BD) region and the hypervariable region 1 (HVR1) of hepatitis C virus (HCV) is described. This method is based on a high-resolution melting (HRM) technique used for genotyping single nucleotide polymorphisms and allows the detection of single nucleotide substitutions in the DNA sequence by measuring its Tm. The modified method, in addition to precisely measuring the Tm, allows the recording of the melting curve of the investigated cDNA fragment, which can provide provisional information about the number of different quasi-species present in the sample. The HRM analysis of the amplified cDNAs encoding the PKR-BD and HVR1 allowed the detection of partial replacement of HCV-1b by HCV-1a subspecies in one of our patients, as well as evaluation of the effectiveness of pegylated interferon α/ribavirin (PEG-IFNα/RBV) therapy. The HRM technique has never been used for the rapid screening of sequence variations in these regions and may be used for a similar purpose in any viral genome.