G-Protein-Coupled Receptor–Membrane Interactions Depend on the Receptor Activation State

G-protein-coupled receptors (GPCRs) are the largest family of human membrane proteins and serve as primary targets of approximately one-third of currently marketed drugs. In particular, adenosine A₁ receptor (A₁AR) is an important therapeutic target for treating cardiac ischemia–reperfusion injuries, neuropathic pain, and renal diseases. As a prototypical GPCR, the A₁AR is located within a phospholipid membrane bilayer and transmits cellular signals by changing between different conformational states. It is important to elucidate the lipid–protein interactions in order to understand the functional mechanism of GPCRs. Here, all-atom simulations using a robust Gaussian accelerated molecular dynamics (GaMD) method were performed on both the inactive (antagonist bound) and active (agonist and G-protein bound) A₁AR, which was embedded in a 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC) lipid bilayer. In the GaMD simulations, the membrane lipids played a key role in stabilizing different conformational states of the A₁AR. Our simulations further identified important regions of the receptor that interacted distinctly with the lipids in highly correlated manner. Activation of the A₁AR led to differential dynamics in the upper and lower leaflets of the lipid bilayer. In summary, GaMD enhanced simulations have revealed strongly coupled dynamics of the GPCR and lipids that depend on the receptor activation state. © 2019 Wiley Periodicals, Inc.     

Transient pockets as mediators of gas molecules routes inside proteins: The case study of dioxygen pathway in homogentisate 1,2-dioxygenase and its implication in Alkaptonuria development

Alkaptonuria (AKU) is an ultra-rare disease caused by mutations in homogentisate 1,2-dioxygenase (HGD) enzyme, characterized by the loss of enzymatic activity and the accumulation of its substrate, homogentisic acid (HGA) in different tissues, leading to ochronosis and organ degeneration. Although the pathological effects of HGD mutations are largely studied, less is known about the structure of the enzyme, in particular the pathways for dioxygen diffusion to the active site, required for the enzymatic reaction, are still uninvestigated. In the present project, the combination of two in silico techniques, Molecular Dynamics (MD) simulation and Implicit Ligand Sampling (ILS), was used to delineate gas diffusion routes in HGD enzyme. A route from the central opening of the hexameric structure of the enzyme to the back of the active site trough the protein moiety was identified as the path for dioxygen diffusion, also overlapping with a transient pocket, which then assumes an important role in dioxygen diffusion. Along the route the sequence location of the missense variant E401Q, responsible for AKU development, was also found, suggesting such mutation to be conducive of enzymatic activity loss by altering the flow dynamics of dioxygen. Our in silico approach allowed also to delineate the route of HGA substrate to the active site, until now only supposed.     

Intersubband absorption in strained AlGaN/GaN double quantum wells

The intersubband absorption of the four-energy-level system in strained AlGaN/GaN double quantum wells is calculated by considering the polarization effect and the strain modification on material parameters (e.g., the conduction band offset, the electron effective mass and the static dielectric constant). It is found that the electron wavefunctions mainly locate at the left well and penetrate into the left barrier. The absorption spectrum exhibits multiple peaks contributed by different transitions. The position and height of absorption peaks are not very sensitive to the structural parameters (i.e., composition and thickness) of the central barrier because of the strong built-in electric field. However, the coupling between two wells can be enhanced by strain modulation.     

On a new class of multiplicative pseudo-random number generators

In the computing literature, there are few detailed analytical studies of the global statistical characteristics of a class of multiplicative pseudo-random number generators.We comment briefly on normal numbers and study analytically the approximately uniform discrete distribution or (j,)-normality in the sense of Besicovitch for complete periods of fractional parts {x _{0 1} ⁱ /p} on [0, 1] fori=0, 1,..., (p–1)p^–1–1, i.e. in current terminology, generators given byx _{n+1 1} x _n mod p wheren=0, 1,..., (p–1)p ^–1–1,p is any odd prime, (x ₀,p)=1, ₁ is a primitive root modp ², and 1 is any positive integer.We derive the expectationsE(X, ),E(X ², ),E(X _nX_n+k); the varianceV(X, ), and the serial correlation coefficient k. By means of Dedekind sums and some results of H. Rademacher, we investigate the asymptotic properties of k for various lagsk and integers 1 and give numerical illustrations. For the frequently used case =1, we find comparable results to estimates of Coveyou and Jansson as well as a mathematical demonstration of a so-called rule of thumb related to the choice of ₁ for small k.Due to the number of parameters in this class of generators, it may be possible to obtain increased control over the statistical behavior of these pseudo-random sequences both analytically as well as computationally.     

HL-1装置边缘区的电探针测量

用一个可移动的静电双探针获得了HL-1装置边缘区电子温度T_e,电子密度n_e的时空分布。实验测得孔栏边缘处T_e和n_e。分别约为12eV和3×10~(11)cm~(-3),n_e沿小半径方向的径向梯度约4.7X 10~(11)cm~(-3);在等离子体边缘区,n_e,T_e的e倍衰减特性长度分别约为20mm和27mm,在删削区内,λ_n,λ_T急剧减小。粒子的横向扩散系数与玻姆系数同量级。     

ΛΛ 6 hypernucleus in α + 2Λ cluster model

The binding energy of the double hypernucleus _ΛΛ ⁶ is calculated in α + 2Λ cluster model using the method of translation invariant basis TIMO. As regards the required interaction potentials we use a density dependent effective ΛN force and a gaussian form for ΛΛ potential. With these interactions a very reasonable value ofB _ΛΛ is obtained if the oscillator states up to the excitation quantum numberN=12 are taken into account in the expansion of wavefunction of the hypernucleus. This value ofN is much smaller than that obtained in an earlier study. This lowering inN value is attributed to a much better choice of ΛN potential used in the present study.     

Effect of ultrasonic power on the stability of low-molecular-weight oyster peptides functional-nutrition W1/O/W2 double emulsion

Ultrasonic-assisted treatment is an eco-friendly and cost-effective emulsification method, and the acoustic cavitation effect produced by ultrasonic equipment is conducive to the formation of stable emulsion. However, its effect on the underlying stability of low-molecular-weight oyster peptides (LOPs) functional-nutrition W₁/O/W₂ double emulsion has not been reported. The effects of different ultrasonic power (50, 75, 100, 125, and 150 W) on the stability of double emulsions and the ability to mask the fishy odor of LOPs were investigated. Low ultrasonic power (50 W and 75 W) treatment failed to form a well-stabilized double emulsion, and excessive ultrasound treatment (150 W) destroyed its structure. At an ultrasonic power of 125 W, smaller particle-sized double emulsion was formed with more uniform distribution, more whiteness, and a lower viscosity coefficient. Meanwhile, the cavitation effect generated by 125 W ultrasonic power improved storage, and oxidative stabilities, emulsifying properties of double emulsion by reducing the droplet size and improved sensorial acceptability by masking the undesirable flavor of LOPs. The structure of the double emulsion was further confirmed by optical microscopy and confocal laser scanning microscopy. The ultrasonic-assisted treatment is of potential value for the industrial application of double emulsion in functional-nutrition foods.     

Multiple re-configurable intelligent surfaces based physical layer eavesdropper detection for V2I communications

Inspired by the promising potential of re-configurable intelligent surface (RIS)-aided transmission in achieving the vision of 6th Generation (6G) network, we analyze the security model for a vehicular-to-infrastructure (V2I) network by considering multiple RISs (M-RIS) on buildings to act as passive relays at fixed distances from a source. In addition, multiple eavesdroppers are presented in the vicinity of the intended destination. Our aim is to enhance the secrecy capacity (SC) and to minimize secrecy outage probability (SOP) in presence of multiple eavesdroppers with the help of M-RIS in V2I communications. We propose a key-less physical layer security using beam-forming by exploiting M-RIS. The proposed approach assumes the concept of detecting eavesdroppers before the information can be transmitted via beam-forming by utilizing M-RIS. The results reveal that with consideration of M-RIS and beam-forming, the achievable SC and SOP performance is significantly improved while imposing minimum power consumption and fewer RIS reflectors.     

Investigation in thorium phosphate by NMR II-phosphorus dipolar networks

With through space and through bond experiments in two-dimensional NMR we analyze the transformation from the thorium phosphate-hydrogen phosphate hydrate (TPHPH) to the β form of the thorium phosphate diphosphate (β-TPD) in relation with the phosphorus networks. These techniques are complementary: the through space coupling gives an insight on the dipolar phosphorus networks while the through bond coupling is particularly efficient in the detection of the P₂O₇ groups. With these experiments we show that in a first step, by heating the precursor TPHPH above 250 °C, it transforms into an form of TPD. This transformation is due to the complete condensation of hydrogen phosphate groups HPO₄ into P₂O₇ entities. By heating -TPD above 950 °C it transforms into its well-known β form. The form is characterized by a hygroscopic behavior: some water molecules are present near the P₂O₇ groups that makes non-equivalent their phosphorus nuclei. PO₄ dipolar networks are always present in the form. The main effect of these PO₄ and P₂O₇ units is to give the system a channel structure and the water enters in them.