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We show that for a subdiffusive continuous time random walk with scale-free waiting time distribution the first-passage dynamics on a finite interval can be optimized by introduction of a piecewise linear potential barrier. Analytical results for the survival probability and first-passage density based on the fractional Fokker-Planck equation are shown to agree well with Monte Carlo simulations results. As an application we discuss an improved design for efficient translocation of gradient copolymers compared to homopolymer translocation in a quasi-equilibrium approximation.
The pre-clinical and clinical development of viral vehicles for gene transfer increased in recent years, and a recombinant adeno-associated virus (rAAV) drug took center stage upon approval in the European Union. However, lack of standardization, inefficient purification methods and complicated retargeting limit general usability. We address these obstacles by fusing rAAV-2 capsids with two modular targeting molecules (DARPin or Affibody) specific for a cancer cell-surface marker (EGFR) while simultaneously including an affinity tag (His-tag) in a surface-exposed loop. Equipping these particles with genes coding for prodrug converting enzymes (thymidine kinase or cytosine deaminase) we demonstrate tumor marker specific transduction and prodrug-dependent apoptosis of cancer cells. Coding terminal and loop modifications in one gene enabled specific and scalable purification. Our genetic parts for viral production adhere to a standardized cloning strategy facilitating rapid prototyping of virus directed enzyme prodrug therapy (VDEPT).
The publication of partial and complete paleogenomes within the last few years has reinvigorated research in ancient DNA. No longer limited to short fragments of mitochondrial DNA, inference of evolutionary processes through time can now be investigated from genome-wide data sampled as far back as 700,000 years. Tremendous insights have been made, in particular regarding the hominin lineage. With rare exception, however, a paleogenomic perspective has been mired by the quality and quantity of recoverable DNA. Though conceptually simple, extracting ancient DNA remains challenging, and sequencing ancient genomes to high coverage remains prohibitively expensive for most laboratories. Still, with improvements in DNA isolation and declining sequencing costs, the taxonomic and geographic purview of paleogenomics is expanding at a rapid pace. With improved capacity to screen large numbers of samples for those with high proportions of endogenous ancient DNA, paleogenomics is poised to become a key technology to better understand recent evolutionary events.
Recently, photosensitive surfactants have re-attracted considerable attention. It has been shown that their association with oppositely charged biologically important polyelectrolytes, such as DNA or microgels, can be efficiently manipulated simply by light exposure. In this article, we investigate the self-assembly of photosensitive surfactants as well as their interactions with DNA by calorimetric and spectroscopic methods. Critical micelle concentration (CMC), standard micellization enthalpy, entropy, and Gibbs energy were determined in different conditions (ionic strengths and temperatures) for a series of cationic surfactants with an azobenzene group in their tail. It is shown, that aggregation forces of photosensitive units play an important role in the micellization giving the major contribution to the micellization enthalpy. The onset of the aggregation can be traced from shift of the absorption peak position in the UV-visible spectrum. Titration UV-visible spectroscopy is used as an alternative, simple, and sensitive approach to estimate CMC. The titration UV-visible spectroscopy was also employed to investigate interactions (CAC: critical aggregation concentration, precipitation, and colloidal stabilization) in the DNA-surfactant complex.
Comparing thermal wave function methods for multi-configuration time-dependent Hartree simulations
(2014)
We compare two methods for creating stochastic temperature wave functions that can be used for Multi-Configuration Time-Dependent Hartree (MCTDH) simulations. In the first method, the MCTDH coefficients are chosen randomly, while the other method uses a single Hartree product of random single-particle functions (SPFs). We find that using random SPFs dramatically improves convergence for a model system for surface sticking.
We have investigated the influence that megathrust earthquake slip has on the activation of splay faults using a 2-D finite element method (FEM), taking into account the effects of gravity and variations in the frictional strength properties of splay faults. We simulated both landward-dipping and seaward-dipping splay fault geometries, and imposed depth-variable slip distributions of subduction events. Our results indicate that the two types of splay fault exhibit a similar behavior, with variations in frictional properties along the faults affecting only the seismic magnitude. The triggering process is controlled by a critical depth. Megathrust slip concentrated at depths shallower than the critical depth will favor normal displacement, while megathrust slip concentrated at depths deeper than the critical depth is likely to result in reverse motion. Our results thus provide a useful tool for predicting the activation of secondary faults and may have direct implications for tsunami hazard research.
The perception of time is a fundamental part of human experience. Recent research suggests that the experience of time emerges from emotional and interoceptive (bodily) states as processed in the insular cortex. Whether there is an interaction between the conscious awareness of interoceptive states and time distortions induced by emotions has rarely been investigated so far. We aimed to address this question by the use of a retrospective time estimation task comparing two groups of participants. One group had a focus on interoceptive states and one had a focus on exteroceptive information while watching film clips depicting fear, amusement and neutral content. Main results were that attention to interoceptive processes significantly affected subjective time experience. Fear was accompanied with subjective time dilation that was more pronounced in the group with interoceptive focus, while amusement led to a quicker passage of time which was also increased by interoceptive focus. We conclude that retrospective temporal distortions are directly influenced by attention to bodily responses. These effects might crucially interact with arousal levels. Sympathetic nervous system activation affecting memory build-up might be the decisive factor influencing retrospective time judgments. Our data substantially extend former research findings underscoring the relevance of interoception for the effects of emotional states on subjective time experience.
In hydrology, the storage-discharge relationship is a fundamental catchment property. Understanding what controls this relationship is at the core of catchment science. To date, there are no direct methods to measure water storage at catchment scales (10(1)-10(3)km(2)). In this study, we use direct measurements of terrestrial water storage dynamics by means of superconducting gravimetry in a small headwater catchment of the Regen River, Germany, to derive empirical storage-discharge relationships in nested catchments of increasing scale. Our results show that the local storage measurements are strongly related to streamflow dynamics at larger scales (> 100km(2); correlation coefficient=0.78-0.81), but at small scale, no such relationship exists (similar to 1km(2); correlation coefficients=-0.11). The geologic setting in the region can explain both the disconnection between local water storage and headwater runoff, and the connectivity between headwater storage and streams draining larger catchment areas. More research is required to understand what controls the form of the observed storage-discharge relationships at the catchment scale. This study demonstrates that high-precision gravimetry can provide new insights into the complex relationship between state and response of hydrological systems.
In this paper a linear-time algorithm for the minimization of acyclic deterministic finite-state automata is presented. The algorithm runs significantly faster than previous algorithms for the same task. This is shown by a comparison of the running times of both algorithms. Additionally, a variation of the new algorithm is presented which handles cyclic automata as input. The new cycle-aware algorithm minimizes acyclic automata in the desired way. In case of cyclic input, the algorithm minimizes all acyclic suffixes of the input automaton.