Piperidines are among the most important synthetic fragments for designing drugs and play a significant role in the pharmaceutical industry. Their derivatives are present in more than twenty classes ...of pharmaceuticals, as well as alkaloids. The current review summarizes recent scientific literature on intra- and intermolecular reactions leading to the formation of various piperidine derivatives: substituted piperidines, spiropiperidines, condensed piperidines, and piperidinones. Moreover, the pharmaceutical applications of synthetic and natural piperidines were covered, as well as the latest scientific advances in the discovery and biological evaluation of potential drugs containing piperidine moiety. This review is designed to help both novice researchers taking their first steps in this field and experienced scientists looking for suitable substrates for the synthesis of biologically active piperidines.
The theory of terahertz (THz) waves generation at the incidence of the focused
p
-polarized laser pulse on the plasma boundary is developed. The angular, spectral, and energy characteristics of the ...THz signal are studied as the function of the focusing degree and the incidence angle of laser radiation, as well as the plasma density. The frequency dependence of the THz signal energy is considered and it is established that the emission spectrum contains the broad line, and its position for tight focusing of laser radiation is determined by its reciprocal duration. The radiation pattern of the THz pulse is studied and it is shown that the decrease in the size of the laser pulse focal spot leads to the increase in the angle of radiation with respect to the normal to the plasma boundary, and for the tight focusing of the laser pulse, THz waves are emitted almost along the plasma-vacuum interface. It is established that the energy of the THz pulse noticeably increases when the
p
-polarized laser pulse is incident almost along the normal onto the near-critical plasma at the angle of total reflection, and the transverse size of the laser pulse decreases. It is shown that the emission of high-power THz pulses with the sufficiently high conversion rate occurs at the almost normal incidence of ultrashort tightly focused laser radiation on the boundary of near-critical plasma with rare electron collisions.
Principles of successful Hamiltonian approaches, which were developed to describe free gravitational field(s) in the metric gravity, are formulated and discussed. By using the standard
Lagrangian
of ...the metric GR we properly introduce all momenta of the metric gravitational field and derive the both canonical
and total
Hamiltonians of the metric GR. We also developed an effective method which is used to determine various Poisson brackets between analytical functions of the basic dynamical variables, i.e., generalized coordinates
and momenta
. In general, such variables can be chosen either from the straight
, or dual
sets of symplectic dynamical variables which always arise (and complete each other) in any Hamiltonian formulation developed for the coupled system of tensor fields. By applying canonical transformation(s) of dynamical variables we reduce the canonical Hamiltonian
to its natural form. The natural form of canonical Hamiltonian provides numerous advantages in actual applications to the metric GR, since the general theory of dynamical systems with such Hamiltonians is well developed. Furthermore, many analytical and numerically exact solutions have been found and described in detail for dynamical systems with the Hamiltonians already reduced to their natural forms. In particular, reduction of the canonical Hamiltonian
to its natural form allows one to derive the Jacobi equation for the free gravitational field(s), which takes a particularly simple form.
Dynamin, best studied for its role in clathrin-mediated endocytosis, is the prototypical member of a family of multidomain GTPases involved in fission and remodeling of multiple organelles. Recent ...studies have shown that dynamin alone can catalyze fission of membrane tubules and vesicle formation from planar lipid templates. Thus, dynamin appears to be a self-sufficient fission machine. Here we review the biochemical activities and structural features of dynamin required for fission activity. As all changes in membrane topology require energetically unfavorable rearrangements of the lipid bilayer, we discuss the interplay between dynamin and its lipid substrates that are critical to defining a nonleaky pathway to membrane fission. We propose a two-stage model for dynamin-catalyzed fission. In stage one, dynamin's mechanochemical activities induce localized curvature stress and position its lipid-interacting pleckstrin homology domains to create a catalytic center that, in stage two, guides lipid remodeling through hemifission intermediates to drive membrane fission.
Quaternary ammonium compounds (QACs) belong to a well-known class of cationic biocides with a broad spectrum of antimicrobial activity. They are used as essential components in surfactants, personal ...hygiene products, cosmetics, softeners, dyes, biological dyes, antiseptics, and disinfectants. Simple but varied in their structure, QACs are divided into several subclasses: Mono-, bis-, multi-, and poly-derivatives. Since the beginning of the 20th century, a significant amount of work has been dedicated to the advancement of this class of biocides. Thus, more than 700 articles on QACs were published only in 2020, according to the modern literature. The structural variability and diverse biological activity of ionic liquids (ILs) make them highly prospective for developing new types of biocides. QACs and ILs bear a common key element in the molecular structure-quaternary positively charged nitrogen atoms within a cyclic or acyclic structural framework. The state-of-the-art research level and paramount demand in modern society recall the rapid development of a new generation of tunable antimicrobials. This review focuses on the main QACs exhibiting antimicrobial and antifungal properties, commercial products based on QACs, and the latest discoveries in QACs and ILs connected with biocide development.
Repeated use of brain-computer interfaces (BCIs) providing contingent sensory feedback of brain activity was recently proposed as a rehabilitation approach to restore motor function after stroke or ...spinal cord lesions. However, there are only a few clinical studies that investigate feasibility and effectiveness of such an approach. Here we report on a placebo-controlled, multicenter clinical trial that investigated whether stroke survivors with severe upper limb (UL) paralysis benefit from 10 BCI training sessions each lasting up to 40 min. A total of 74 patients participated: median time since stroke is 8 months, 25 and 75% quartiles 3.0; 13.0; median severity of UL paralysis is 4.5 points 0.0; 30.0 as measured by the Action Research Arm Test, ARAT, and 19.5 points 11.0; 40.0 as measured by the Fugl-Meyer Motor Assessment, FMMA. Patients in the BCI group (
= 55) performed motor imagery of opening their affected hand. Motor imagery-related brain electroencephalographic activity was translated into contingent hand exoskeleton-driven opening movements of the affected hand. In a control group (
= 19), hand exoskeleton-driven opening movements of the affected hand were independent of brain electroencephalographic activity. Evaluation of the UL clinical assessments indicated that both groups improved, but only the BCI group showed an improvement in the ARAT's grasp score from 0 0.0; 14.0 to 3.0 0.0; 15.0 points (
< 0.01) and pinch scores from 0.0 0.0; 7.0 to 1.0 0.0; 12.0 points (
< 0.01). Upon training completion, 21.8% and 36.4% of the patients in the BCI group improved their ARAT and FMMA scores respectively. The corresponding numbers for the control group were 5.1% (ARAT) and 15.8% (FMMA). These results suggests that adding BCI control to exoskeleton-assisted physical therapy can improve post-stroke rehabilitation outcomes. Both maximum and mean values of the percentage of successfully decoded imagery-related EEG activity, were higher than chance level. A correlation between the classification accuracy and the improvement in the upper extremity function was found. An improvement of motor function was found for patients with different duration, severity and location of the stroke.
The article presents the results of dynamic-stochastic modeling of long-term variations of Caspian Sea level during the Early khvalyn (Buinak stage) and the Late khvalyn (Makhachkala stage) ...transgressions. A linearized model of Caspian level variations with a negative feedback due to the dependence of sea water area on water level is shown to be applicable to the paleo-Caspian. The calculations were based on the results of simulation and analytical modeling. The regimes of long-term level variations in the paleo-Caspian Sea for the considered transgressions are shown to differ. For example, the variance of the Caspian Sea level for the Early and Late khvalyn transgressions is equal to 4.2 and 2.5 m
2
, respectively, and the average duration of the level rise above its equilibrium value during a single event is ~50 and ~40 years, respectively. Estimates of the duration of sea level rises can be used to assess the possibility of formation of various coastal–shelf geomorphological forms during long-term level rises. The obtained characteristics of the processes of long-term sea level variations, including the variance, autocorrelation, probability distribution density, the mean duration of level rises above (or level drops below) specified level marks during one such event, the dependence of the parameter of inertia of level variations significantly expand our knowledge about the character of Caspian Sea level variations in the paleotime.
The large GTPase dynamin is the first protein shown to catalyze membrane fission. Dynamin and its related proteins are essential to many cell functions, from endocytosis to organelle division and ...fusion, and it plays a critical role in many physiological functions such as synaptic transmission and muscle contraction. Research of the past three decades has focused on understanding how dynamin works. In this review, we present the basis for an emerging consensus on how dynamin functions. Three properties of dynamin are strongly supported by experimental data: first, dynamin oligomerizes into a helical polymer; second, dynamin oligomer constricts in the presence of GTP; and third, dynamin catalyzes membrane fission upon GTP hydrolysis. We present the two current models for fission, essentially diverging in how GTP energy is spent. We further discuss how future research might solve the remaining open questions presently under discussion.
This consensus review summarizes our current understanding of the function of the fission GTPase dynamin and highlights open questions in the field.
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