442 research outputs found

    Permeation Mechanism of Potassium Ions through the Large Conductance Ca2+-Activated Potassium Channel

    Get PDF
    The permeation of the potassium ion (K+) through the selectivity filter (SF) of the large conductance Ca2+-activated potassium (Slo1) channel remains an interesting question to study. Although the mode of K+ entering and leaving the SF has been revealed, the mechanism of K+ passing through the SF is still not clear. In the present study, the pattern of K+ permeation through the SF is investigated by chemical computation and data mining based on the molecular structure of Slo1 from Aplysia californica. Both bond configurations and the free energy of K+s inside the SF was studied using Discovery Studio software. The results suggested that, to accommodate increasing energy levels and to tolerate more K+s, 4-fold symmetric subunits of SF can only move at one direction that is perpendicular to the center axis. In addition, two configurations of chemical bonds between K+s and the SF are usually employed including the chelate configuration under low free energy and the complex configuration under high free energy conditions. Moreover, three patterns of bond configurations for multiple K+s within the SF are used to accommodate the energetic changes of the SF, and each pattern is composed of one or two subconformations. These findings likely resulted from the evolutionary optimization of the protein function of Slo1. The specific conductance and the voltage-gating of the Slo1 channel can be reinterpreted with the permeation mechanism of K+s found in the current study. The permeation mechanism of K+s through the SF can be used to understand the interaction between various toxins and the Slo1 channel, and can be employed to develop new drugs targeting relevant ion channels

    Modal Strain Based Method for Dynamic Design of Plate-Like Structures

    Get PDF
    Design optimization of dynamic properties, for example, modal frequencies, can be of much importance when structures are exposed to the shock and/or vibration environments. A modal strain based method is proposed for fast design of natural frequencies of plate-like structures. The basic theory of modal strains of thin plates is reviewed. The capability of determining the highly sensitive elements by means of modal strain analysis is theoretically demonstrated. Finite element models were constructed in numerical simulations. Firstly, the application of the proposed method is conducted on a central-massed flat plate which was topologically optimized by the Reference. The results of modal strain analysis at the first mode have good agreement with the results from the topology optimization. Furthermore, some features of the strain mode shapes (SMSs) of the flat plate are investigated. Finally, the SMSs are applied to the optimization of a stiffened plate. Attention is focused on the distributions of the SMSs of the stiffeners, which also shows good agreement with the results from the topology optimization in the previous study. Several higher orders of SMSs are extracted, which can visualize the most sensitive elements to the corresponding modal frequency. In summary, both the theory and simulations validate the correctness and convenience of applying SMSs to dynamic design of plate-like structures

    Modal Strain Based Method for Dynamic Design of Plate-Like Structures

    Get PDF
    Design optimization of dynamic properties, for example, modal frequencies, can be of much importance when structures are exposed to the shock and/or vibration environments. A modal strain based method is proposed for fast design of natural frequencies of plate-like structures. The basic theory of modal strains of thin plates is reviewed. The capability of determining the highly sensitive elements by means of modal strain analysis is theoretically demonstrated. Finite element models were constructed in numerical simulations. Firstly, the application of the proposed method is conducted on a central-massed flat plate which was topologically optimized by the Reference. The results of modal strain analysis at the first mode have good agreement with the results from the topology optimization. Furthermore, some features of the strain mode shapes (SMSs) of the flat plate are investigated. Finally, the SMSs are applied to the optimization of a stiffened plate. Attention is focused on the distributions of the SMSs of the stiffeners, which also shows good agreement with the results from the topology optimization in the previous study. Several higher orders of SMSs are extracted, which can visualize the most sensitive elements to the corresponding modal frequency. In summary, both the theory and simulations validate the correctness and convenience of applying SMSs to dynamic design of plate-like structures

    Modal Strain Based Method for Dynamic Design of Plate-Like Structures

    Get PDF
    Design optimization of dynamic properties, for example, modal frequencies, can be of much importance when structures are exposed to the shock and/or vibration environments. A modal strain based method is proposed for fast design of natural frequencies of plate-like structures. The basic theory of modal strains of thin plates is reviewed. The capability of determining the highly sensitive elements by means of modal strain analysis is theoretically demonstrated. Finite element models were constructed in numerical simulations. Firstly, the application of the proposed method is conducted on a central-massed flat plate which was topologically optimized by the Reference. The results of modal strain analysis at the first mode have good agreement with the results from the topology optimization. Furthermore, some features of the strain mode shapes (SMSs) of the flat plate are investigated. Finally, the SMSs are applied to the optimization of a stiffened plate. Attention is focused on the distributions of the SMSs of the stiffeners, which also shows good agreement with the results from the topology optimization in the previous study. Several higher orders of SMSs are extracted, which can visualize the most sensitive elements to the corresponding modal frequency. In summary, both the theory and simulations validate the correctness and convenience of applying SMSs to dynamic design of plate-like structures

    Tetra­aqua­bis­[1-(3-carb­oxy­phen­yl)-4,4′-bipyridin-1-ium-κN 1′]zinc bis­(4,5-carb­oxy­benzene-1,2-dicarboxyl­ate) 2.5-hydrate

    Get PDF
    In the complex cation of the title compound, [Zn(C17H13N2O2)2(H2O)4](C10H4O8)2·2.5H2O, the ZnII atom, lying on an inversion center, is coordinated by two N atoms from two N-(3-carb­oxy­phen­yl)-4,4′-bipyridin-1-ium ligands and four water mol­ecules in a distorted octa­hedral geometry. The pyromellitate anion is double deprotonated. O—H⋯O and C—H⋯O hydrogen bonds connect the cations, anions and uncoordinated water mol­ecules into a three-dimensional supra­molecular network. One of the two lattice water molecules shows an occupancy of 0.25. An intra­molecular O—H⋯O hydrogen bond is present in the anion

    Effects of oxycodone hydrochloride and dezocine on hemodynamics and levels of inflammatory factors in patients receiving gynecological laparoscopic surgery under general anesthesia

    Get PDF
    We aimed to compare the effects of oxycodone hydrochloride and dezocine on hemodynamics and inflammatory factors in patients receiving gynecological laparoscopic surgery under general anesthesia. A total of 246 patients were divided into group A and B (n=123). Hemorheology indices were recorded 5 min after anesthesia (T0), 1 min after pneumoperitoneum (T1), when position was changed 5 min after pneumoperitoneum (T2), 15 min after pneumoperitoneum (T3), 1 min (T4) and 5 min (T5) after position was restored. Visual analogue scale scores 1, 2, 6, 12, 24 and 48 h after operation were recorded. Postoperative adverse reactions and visceral pain were observed. The expression levels of inflammatory factors were detected by enzyme-linked immunosorbent assay 12 h after operation. Compared with group A, group B had higher heart rate and mean arterial pressure at T2, lower central venous pressure and cardiac output at T1-T3, and higher systemic vascular resistance at T1-T5 (P<0.05). The incidence rate of pain syndrome in group A was lower (P<0.05). Group A had lower tumor necrosis factor-alpha and interleukin-6 expression levels and higher interleukin-10 level than those of group B (P<0.05). For gynecological laparoscopic surgery, oxycodone preemptive analgesia has superior outcomes to those of dezocine

    Application of Potential Theory to Steady Flow Past Two Cylinders in Tandem Arrangement

    Get PDF
    The wake flow patterns associated with flow past a cylinder and a cylinder-pair in tandem configuration are revisited, compared, and evaluated with respect to the streamline patterns generated based on potential flow theory and superposition of various potential flow elements. The wakes, which are vortex shedding in the lee of the cylinder(s), are reproduced by placing pairs of equal but opposite circulation elements in the potential flow field. The strength of the circulation elements determines the size of the vortices produced. The streamline patterns of flow past a pair of unequal cylinders in tandem configuration provide an indirect means to establish the threshold condition for the wake transition from that of a single bluff body to alternating reattachment behavior. This threshold condition is found to be a function of the diameter ratio, d/D (diameters d and D, d≤D ), spacing ratio, L/D (centre-to-centre distance, L, to cylinder diameter, D), and equivalent incident flow speed, U. A unique functional relationship f (L/D, d/D, U) of this threshold condition is established

    CCL2/CCR2 signaling elicits itch- and pain-like behavior in a murine model of allergic contact dermatitis

    Get PDF
    Spontaneous itch and pain are the most common symptoms in various skin diseases, including allergic contact dermatitis (ACD). The chemokine (C-C motif) ligand 2 (CCL2, also referred to as monocyte chemoattractant protein 1 (MCP-1)) and its receptor CCR2 are involved in the pathophysiology of ACD, but little is known of the role of CCL2/CCR2 for the itch- and pain-behaviors accompanying the murine model of this disorder, termed contact hypersensitivity (CHS). C57BL/6 mice previously sensitized to the hapten, squaric acid dibutyl ester, applied to the abdomen were subsequently challenged twice with the hapten delivered to either the cheek or to the hairy skin of the hind paw resulting in CHS at that site. By 24 h after the 2nd challenge to the hind paw CCL2 and CCR2 mRNA, protein, and signaling activity were upregulated in the dorsal root ganglion (DRG). Calcium imaging and whole-cell current-clamp recordings revealed that CCL2 directly acted on its neuronal receptor, CCR2 to activate a subset of small-diameter, nociceptive-like DRG neurons retrogradely labeled from the CHS site. Intradermal injection of CCL2 into the site of CHS on the cheek evoked site-directed itch- and pain-like behaviors which could be attenuated by prior delivery of an antagonist of CCR2. In contrast, CCL2 failed to elicit either type of behavior in control mice. Results are consistent with the hypothesis that CHS upregulates CCL2/CCR2 signaling in a subpopulation of cutaneous small diameter DRG neurons and that CCL2 can activate these neurons through neuronal CCR2 to elicit itch- and pain-behavior. Targeting the CCL2/CCR2 signaling might be beneficial for the treatment of the itch and pain sensations accompanying ACD in humans

    Research progress on alternative kombucha substrate transformation and the resulting active components

    Get PDF
    Kombucha is a customary tea-based beverage that is produced through the process of fermenting a mixture of tea and sugar water with symbiotic culture of bacteria and yeast (SCOBY). Traditional kombucha has various beneficial effects and can improve immunity. The significant market share of Kombucha can be attributed to the growing consumer inclination towards healthy foods within the functional beverage industry. The research focus has recently expanded from the probiotics of traditional black tea kombucha to encompass other teas, Chinese herbs, plant materials, and alternative substrates. There is a lack of comprehensive literature reviews focusing on substance transformation, functional, active substances, and efficacy mechanisms of alternative kombucha substrates. This article aimed to bridge this gap by providing an in-depth review of the biological transformation pathways of kombucha metabolites and alternative substrates. The review offers valuable insights into kombucha research, including substance metabolism and transformation, efficacy, pharmacological mechanism, and the purification of active components, offering direction and focus for further studies in this field
    • …
    corecore