The Problem of Positive and Destructive Freedom: The Interpretation of the Arkady Svidrigailov Image

This article examines the problem of the relationship between freedom and self-will on the example of one of the heroes of Dostoevskys novel Crime and Punishment . Attention is focused not only on the canonical text of the novel, but also on the preparatory materials for it. The task is to identify the connection between the above named problem and the suicide problem of Arkady Ivanovich Svidrigailov. The thesis is put forward that for Dostoevskys heroes, self-will often becomes a fetter for their own nature and their own passions. With the help of debauchery, Svidrigailov tries to assert himself, giving his soul to the mercy of willfulness. There is a certain pattern in the fact that such a worldview logical chain ends with the tragic act of suicide. Arkady Ivanovich adores comfort, and therefore, in accordance with his own logic, his murder by Dunya, which did not happen, can be considered, among other things, as an attempt of a comfortable method of suicide. In the preparatory materials for the novel, Svidrigailov protests against cowardly meanness and puts suicide above such a humiliating state, although he understands the entire flaw in such a situation. For all the complexities the problem of freedom and self-will - one of the leitmotifs of religious and philosophical themes in the writers work - Dostoevsky does not see its formal, external solution.

Constrained Multi-Objective Optimization of Simulated Tree Pruning with Heterogeneous Criteria

Virtual pruning of simulated fruit tree models is a useful functionality provided by software tools for computer-aided horticultural education and research. It also enables algorithmic pruning optimization with respect to a set of quantitative objectives, which is important for analytical purposes and potential applications in automated pruning. However, the existing studies in pruning optimization focus on a single type of objective, such as light distribution within the crown. In this paper, we propose the use of heterogeneous objectives for discrete multi-objective optimization of simulated tree pruning. In particular, the average light intake, crown shape, and tree balance are used to observe the emergence of different pruning patterns in the non-dominated solution sets. We also propose the use of independent constraint objectives as a new mechanism to confine overfitting of solutions to individual pruning criteria. Finally, we perform the comparison of NSGA-II, SPEA2, and MOEA/D-EAM on this task. The results demonstrate that SPEA2 and MOEA/D-EAM, which use external solution archives, can produce better sets of non-dominated solutions than NSGA-II.

Singularly Perturbed Solutions for a Class of Thermoelastic Weakly Coupled Problems

Based on the basic equation of Green Lindsay (G-L) theory, the thermoelastic weak coupling problem under the basic equation is discussed, that is, two thermal relaxation parameters are added to the constitutive equation, the influence of the coupling term on the temperature field and elastic field is considered, and the asymptotic solution of the governing equation is constructed. Firstly, in order to obtain the asymptotic solution, the singularly perturbed expansion method is used.Then,combined with the corresponding boundary conditions, the partial differential equation method is used to solve the external solution and the boundary layer correction term. Secondly, in the case of weak coupling, the uniformly efficient estimation of the remainder of the asymptotic solution is obtained by using Gronwall inequality, so as to obtain the uniformly efficient of the formal asymptotic solution. Finally, the first term of the asymptotic solution is numerically analyzed by using the singularly perturbed numerical method. The present work will be conducive to the analysis of thermoelastic processes and numerical simulation of different materials in the case of weak coupling.

Generalization of Vaidya’s Metric for A Radiating Star to Rotating Star

Schwarzschild's external solution of Einstein’s gravitational field equations in the general theory of relativity for a static star has been generalized by Vaidya [1], taking into account the radiation of the star. Here, we generalize Vaidya’s metric to a star that is rotating and radiating. Although, there is a famous Kerr solution [2] for a rotating star, but here is a simple solution for a rotating star which may be termed as a zero approximate version of the Kerr solution. Results are discussed.

3D Printing of Thermoresponsive Hydrogel Laden with an Antimicrobial Agent towards Wound Healing Applications

Thermoresponsive hydrogel-based wound dressings with an incorporated antimicrobial agent can be fabricated employing 3D printing technology. A novel printable ink containing poly(N-isopropylacrylamide) (PNIPAAm) precursors, sodium alginate (ALG), methylcellulose (MC) that is laden with a mixture of octenidine dihydrochloride and 2-phenoxyethanol (Octenisept®, OCT) possess accurate printability and shape fidelity. This study also provides the protocol of ink’s use for the 3D printing of hydrogel scaffolds. The hydrogel’s physicochemical properties and drug release profiles from the hydrogel specimens to the external solution have been determined at two temperatures (20 and 37 °C). The release test showed a sustained OCT delivery into ultrapure water and the PBS solution. The temperature-responsive hydrogel exhibited antimicrobial activity against Staphylococcus aureus, Candida albicans, and Pseudomonas aeruginosa and demonstrated non-cytotoxicity towards fibroblasts. The thermoresponsive behavior along with biocompatibility, antimicrobial activity, and controlled drug release make this hydrogel a promising class of materials for wound dressing applications.

Shaker-IR K+ channel gating in heavy water: Role of structural water molecules in inactivation

It has been reported earlier that the slow (C-type) inactivated conformation in Kv channels is stabilized by a multipoint hydrogen-bond network behind the selectivity filter. Furthermore, MD simulations revealed that structural water molecules are also involved in the formation of this network locking the selectivity filter in its inactive conformation. We found that the application of an extracellular, but not intracellular, solution based on heavy water (D2O) dramatically slowed entry into the slow inactivated state in Shaker-IR mutants (T449A, T449A/I470A, and T449K/I470C, displaying a wide range of inactivation kinetics), consistent with the proposed effect of the dynamics of structural water molecules on the conformational stability of the selectivity filter. Alternative hypotheses capable of explaining the observed effects of D2O were examined. Increased viscosity of the external solution mimicked by the addition of glycerol had a negligible effect on the rate of inactivation. In addition, the inactivation time constants of K+ currents in the outward and the inward directions in asymmetric solutions were not affected by a H2O/D2O exchange, negating an indirect effect of D2O on the rate of K+ rehydration. The elimination of the nonspecific effects of D2O on our macroscopic current measurements supports the hypothesis that the rate of structural water exchange at the region behind the selectivity filter determines the rate of slow inactivation, as proposed by molecular modeling.

Low-voltage activated (LVA) inward current in murine antral smooth muscle cells is an artifact

We characterized the two types of voltage-dependent inward currents in murine antral SMC. The HVA and LVA inward currents were identified when cells were bathed in Ca2+-containing physiological salt solution. We examined whether the LVA inward current was due to: 1) T-type Ca2+ channels, 2) Ca2+-activated Cl- channels, 3) non-selective cation channels (NSCC) or 4) voltage-dependent K+ channels with internal Cs+-rich solution. Replacement of external Ca2+ (2 mM) with equimolar Ba2+ increased the amplitude of the HVA current but blocked the LVA current. Nicardipine blocked the HVA current, and in the presence of nicardipine, T-type Ca2+ blockers failed to block LVA. The Cl- channel antagonist had little effect on LVA. Cation-free external solution completely abolished both HVA and LVA. Addition of Ca2+ in cation-free solution restored only HVA currents. Addition of K+ (5 mM) to cation-free solution induced LVA current that reversed at -20 mV. These data suggest that LVA is not due to T-type Ca2+ channels, Ca2+-activated Cl- channels or NSCC. Antral SMC express A-type K+ currents (KA) and delayed rectifying K+ currents (KV) with dialysis of high K+ (140 mM) solution. When cells were exposed to high K+ external solution with dialysis of Cs+-rich solution in the presence of nicardipine, LVA was evoked and reversed at positive potentials. These HK-induced inward currents were blocked by K+ channel blockers, 4-aminopyridine and TEA. In conclusion, LVA inward currents can be generated by K+ influx via KA and KV channels in murine antral SMC when cells were dialyzed with Cs+-rich solution.

Phospholipid membrane formation templated by coacervate droplets

We report formation of coacervate-supported phospholipid membranes by hydrating a dried lipid film in the presence of coacervate droplets. In contrast to traditional giant lipid vesicles formed by gentle hydration in the absence of coacervates, the coacervate-templated membrane vesicles are more uniform in size, shape, and apparent lamellarity. Due to their fully-coacervate model cytoplasm, these simple artificial cells are macromolecularly crowded and can be easily pre-loaded with high concentrations of proteins or nucleic acids. Coacervate-supported membranes were characterized by fluorescence imaging, polarization, fluorescence recovery after photobleaching of labeled lipids, lipid quenching experiments, and solute uptake experiments. Our findings are consistent with the presence of lipid membranes around the coacervates, with many droplets fully coated with what appear to be continuous lipid bilayers. Within the same population, other coacervate droplets are coated with membranes having defects or pores that permit solute entry, and still others are coated with multilayered membranes. These membranes surrounding protein-based coacervate droplets provided protection from a protease added to the external solution. The simplicity of producing artificial cells having a coacervate model cytoplasm surrounded by a model membrane is at the same time interesting as a potential mechanism for prebiotic protocell formation and appealing for biotechnology. We anticipate that such structures could serve as a new type of model system for understanding interactions between intracellular phases and cell- or organelle membranes, which are implicated in a growing number of processes ranging from neurotransmission to signaling.

Ca2+ signaling driving pacemaker activity in submucosal interstitial cells of Cajal in the murine colon

Interstitial cells of Cajal (ICC) generate pacemaker activity responsible for phasic contractions in colonic segmentation and peristalsis. ICC along the submucosal border (ICC-SM) contribute to mixing and more complex patterns of colonic motility. We show the complex patterns of Ca2+ signaling in ICC-SM and the relationship between ICC-SM Ca2+ transients and activation of SMCs using optogenetic tools. ICC-SM displayed rhythmic firing of Ca2+ transients ~15 cpm and paced adjacent SMCs. The majority of spontaneous activity occurred in regular Ca2+ transients clusters (CTCs) that propagated through the network. CTCs were organized and dependent upon Ca2+ entry through voltage-dependent Ca2+ conductances, L- and T-type Ca2+ channels. Removal of Ca2+ from the external solution abolished CTCs. Ca2+ release mechanisms reduced the duration and amplitude of Ca2+ transients but did not block CTCs. These data reveal how colonic pacemaker ICC-SM exhibit complex Ca2+ firing patterns and drive smooth muscle activity and overall colonic contractions.