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Pyrazinamidase (PZase) is a member of Fe-dependent amidohydrolases that activates pyrazinamide (PZA) into active pyrazinoic acid (POA). PZA, a nicotinamide analogue, is an essential first-line drug...

G-protein-coupled receptor 142 (GPR142) belongs to rhodopsin family. GPR142 and GPR119, both Gq-coupled receptors, are expressed in pancreatic β cells of pancreas; their activation eventually leads to triggering of insulin secretion. In this paper, through a systems and synthetic biology approach, the effect of a common hit compound has been investigated in GPR142 and GPR119 pathways. This hit that has the potential to be developed as a lead for nanodrug was obtained through high-throughput virtual screening. The hit compound was further docked with nanoparticles (GOLD, SPION, and CeO2). The probable effect of this potential hit on insulin secretion in type 2 diabetes and its dynamic behavior was explored. Kinetic simulation was performed for cross-validation of its role in both the pathways. This study opens up a probable avenue in therapy of type 2 diabetes through regulation of GPR142 and GPR119 receptors. The biological circuit constructed may further have an application as a modulator to control the up- and downregulation of the biochemical pathway and can be implemented as sensors or nanochips for therapy.

The authors have requested that this preprint be removed from Research Square.

Colorectal cancer is considered one of the leading causes of death that is linked with the Kirsten Rat Sarcoma (

The Linghu Au deposit is located within the northeastern part of the Xiaoqinling region in the southern margin of the North China Craton. Field investigations, cross-cutting relationships, and mineral paragenetic associations have identified three stages of hydrothermal activity. To determine the origin and evolution of ore-forming fluids, and better understand genesis of the Linghu Au deposit, we have undertaken a series of studies including fluid inclusion and He–Ar–H–O–S–Pb isotope systematics. Fluid inclusion study indicates that the early stage of gold mineralization was characterized by a high-temperature and low-salinity H2O–CO2–NaCl hydrothermal fluids that have δD values of – 82.0 to – 78.6‰ and δ18OH2O values of 5.3 to 6.4‰. The intermediate stage of gold mineralization involved moderate temperature H2O–CO2–NaCl hydrothermal fluids with δD and δ18OH2O values of – 92.7‰ to – 87.9‰ and – 1.4‰ to 0‰, respectively. Pyrite samples from this mineralization stage have 3He/4He and 40Ar/36Ar ratios of 0.26–0.31 Ra and 2834.7–4300.6, respectively. The last mineralization stage involved (low-temperature and low-salinity NaCl–H2O system of hydrothermal fluids with relatively lower δD values of – 93.1 to – 92.3‰ and δ18OH2O values of – 5.7 to – 5.2‰. Moreover, sulfides in ores yielded δ34S values of – 3.6 to 5.9‰, with an average of 2.65‰. The sulfides have 206Pb/204Pb ratios of 17.101–17.804, 207Pb/204Pb ratios of 15.438–15.554, and 208Pb/204Pb ratios of 37.438–38.654. The results of fluid inclusions and H–O, S–Pb, and He–Ar isotopes indicate that hydrothermal fluids associated with the early stage of mineralization originated from magmatic fluids, with sulfur and lead being derived from both units of the Taihua Group and a Late Triassic magmatic–hydrothermal system. All of these data indicate that the Linghu gold deposit formed as a result of magmatic–hydrothermal mineralizing processes.

Pyrazinamidase (PZase) is a member of Fe-dependent amidohydrolases that activates pyrazinamide (PZA) into active pyrazinoic acid (POA). PZA, a nicotinamide analogue, is an essential first-line drug used in

Helicobacter pylori (H. pylori) is one of the most extensively studied Gram-negative bacteria due to its implication in gastric cancer. The oncogenicity of H. pylori is associated with cytotoxin-associated gene A (CagA), which is injected into epithelial cells lining the stomach. Both the C- and N-termini of CagA are involved in the interaction with several host proteins, thereby disrupting vital cellular functions, such as cell adhesion, cell cycle, intracellular signal transduction, and cytoskeletal structure. The N-terminus of CagA interacts with the tumor-suppressing protein, apoptosis-stimulating protein of p53 (ASPP2), subsequently disrupting the apoptotic function of tumor suppressor gene p53. Here, we present the in-depth molecular dynamic mechanism of the CagA–ASPP2 interaction and highlight hot-spot residues through in silico mutagenesis. Our findings are in agreement with previous studies and further suggest other residues that are crucial for the CagA–ASPP2 interaction. Furthermore, the ASPP2-binding pocket possesses potential druggability and could be engaged by decoy peptides, identified through a machine-learning system and suggested in this study. The binding affinities of these peptides with CagA were monitored through extensive computational procedures and reported herein. While CagA is crucial for the oncogenicity of H. pylori, our designed peptides possess the potential to inhibit CagA and restore the tumor suppressor function of ASPP2.

Papermaking technique was applied to fabricate the centrifuged glassfiber mat (CGM). This paper discussed the influence of the number of beating revolutions on the morphology, drainability and abso...

A drug may be metabolized by multiple cytochrome P450 (CYP450) isoforms. Predicting the metabolic fate of drugs is very important to prevent drug-drug interactions in the development of novel pharmaceuticals. Prediction of CYP450 enzyme-substrate selectivity is formulized as a multilabel learning task in this study. First, we compared the performance of feature combinations based on four different categories of features, which are physiochemical property descriptors, mol2vec descriptors, extended connectivity fingerprints, and molecular access system key fingerprints on modeling. After identifying the best combination of features, we applied seven different multilabel models, which are multilabel

G protein-coupled receptor 15 (GPR15, also known as BOB) is an extensively studied orphan G protein-coupled receptors (GPCRs) involving human immunodeficiency virus (HIV) infection, colonic inflammation, and smoking-related diseases. Recently, GPR15 was deorphanized and its corresponding natural ligand demonstrated an ability to inhibit cancer cell growth. However, no study reported the potential role of GPR15 in a pan-cancer manner. Using large-scale publicly available data from the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases, we found that GPR15 expression is significantly lower in colon adenocarcinoma (COAD) and rectal adenocarcinoma (READ) than in normal tissues. Among 33 cancer types, GPR15 expression was significantly positively correlated with the prognoses of COAD, neck squamous carcinoma (HNSC), and lung adenocarcinoma (LUAD) and significantly negatively correlated with stomach adenocarcinoma (STAD). This study also revealed that commonly upregulated gene sets in the high GPR15 expression group (stratified via median) of COAD, HNSC, LUAD, and STAD are enriched in immune systems, indicating that GPR15 might be considered as a potential target for cancer immunotherapy. Furthermore, we modelled the 3D structure of GPR15 and conducted structure-based virtual screening. The top eight hit compounds were screened and then subjected to molecular dynamics (MD) simulation for stability analysis. Our study provides novel insights into the role of GPR15 in a pan-cancer manner and discovered a potential hit compound for GPR15 antagonists.

Rivaroxaban (RIV) is a direct oral anticoagulant (DOAC) targeting activated coagulation factor X (FXa). An earlier study reported the F174A mutant of FXa resistant to a RIV-like inhibitor, Apixaban. In current study, the detailed molecular mechanism of the resistance has been explored by molecular dynamics simulations on the impaired interactions between RIV and FXa in the damaged S4 pocket of F174A mutant. Besides, an unexpected relative stable binding mode of S1'S1 was revealed, which required dynamic motions of Gln192 and Gln61 to allow the morpholinone moiety of RIV to shift into the S1' pocket and form strong interactions. These dynamic motions of RIV and critical residues might be important in drug design for direct inhibitors of coagulation factors.

Half of the world population is infected by the Gram-negative bacterium Helicobacter pylori (H. pylori). It colonizes in the stomach and is associated with severe gastric pathologies including gastric cancer and peptic ulceration. The most virulent factor of H. pylori is the cytotoxin-associated gene A (CagA) that is injected into the host cell. CagA interacts with several host proteins and alters their function, thereby causing several diseases. The most well-known target of CagA is the tumor suppressor protein ASPP2. The subdomain I at the N-terminus of CagA interacts with the proline-rich motif of ASPP2. Here, in this study, we carried out alanine scanning mutagenesis and an extensive molecular dynamics simulation summing up to 3.8 μs to find out hot spot residues and discovered some new protein-protein interaction (PPI)-modulating molecules. Our findings are in line with previous biochemical studies and further suggested new residues that are crucial for binding. The alanine scanning showed that mutation of Y207 and T211 residues to alanine decreased the binding affinity. Likewise, dynamics simulation and molecular mechanics with generalized Born surface area (MMGBSA) analysis also showed the importance of these two residues at the interface. A four-feature pharmacophore model was developed based on these two residues, and top 10 molecules were filtered from ZINC, NCI, and ChEMBL databases. The good binding affinity of the CHEMBL17319 and CHEMBL1183979 molecules shows the reliability of our adopted protocol for binding hot spot residues. We believe that our study provides a new insight for using CagA as the therapeutic target for gastric cancer treatment and provides a platform for a future experimental study.

Novel fiber/powder hybrid core materials (HCMs) containing various combination ratios of fumed silica (FS), rice husk ash (RHA), carbon black, titanium dioxide and polyester chopped strand were prepared by dry powder mixing method. The HCMs and their corresponding vacuum insulation panel (VIP) samples were thoroughly characterized to get insight information about their microstructures, structural stability and thermal conductivities. The results revealed that the HCMs possessed a hierarchical meso-/macro-structure with a high porosity of 80.5–87.9% and a fine pore size of 150.9–210.3 nm. Both compression and rebound ratios of the VIPs initially increased (up to ~59%) with the increasing RHA content and thereafter decreased till 39% and 31% respectively. The initial total thermal conductivities of the VIPs were ~5.5 mW/(m K), which increased with the increasing RHA content as well. The proposed VIPs possessed not only a low total thermal conductivity (at 100–100,000 Pa) in between that of glassfiber-VIPs and opacified FS-VIPs but also a much longer service life than glassfiber-VIPs. The addition of 36 wt.% RHA resulted in a 32% reduction in the cost of HCMs, while still maintaining its super insulation capability. The optimum RHA content that led to a low-cost and highly thermal efficient VIP was 26–36 wt.%. Keywords: Vacuum insulation panel, Hybrid core material, Pore structure, Compression behavior, Thermal conductivity, Low cost

The LaF3-coated Li[Li0.2Mn0.54Ni0.13Co0.13]O2 nanoparticles were synthesized via co-precipitation method followed by simple chemical deposition process. The crystal structure, particle morphology, and electrochemical properties of the bare and coated materials were studied by XRD, SEM, TEM, charge–discharge tests. The results showed that the surface coating on Li[Li0.2Mn0.54Ni0.13Co0.13]O2 nanoparticles were amorphous LaF3 layer with a thickness of about 10–30 nm. After the surface modification with LaF3 films, the coating layer served as a protective layer to suppress the side reaction between the positive electrode and electrolyte, and the Li[Li0.2Mn0.54Ni0.13Co0.13]O2 oxide demonstrated the improved electrochemical properties. The LaF3-coated Li[Li0.2Mn0.54Ni0.13Co0.13]O2 electrode delivered the capacities of 270.5, 247.9, 197.1, 170.0, 142.7, and 109.5 mAh g−1 at current rates of 0.1, 0.2, 0.5, 1, 2, and 5 C rate, respectively. Besides, the capacity retention was increased from 85.1 to 94.8 % after 100 cycles at 0.5 C rate. It implied surface modification with LaF3 played an important role to improve the cyclic stability and rate capacity of the Li-rich nickel manganese oxides.

The FeF3-coated Li[Li0.2Mn0.54Ni0.13Co0.13]O2 cathode materials were synthesized via a wet chemical process followed by a solid state reaction. The physical properties of the as-prepared samples were conducted using X-ray diffraction, scanning electron microscopy, and transmission electron microscopy. The results indicated that the surface of cathode particles was covered by FeF3 film (about 5–15 nm thick). Compared with the bare cathode, the FeF3-coated Li[Li0.2Mn0.54Ni0.13Co0.13]O2 one delivered the higher coulombic efficiency, better rate capability, longer cycle life, and better structure stability. A high capacity retention of 95% (190 mAh g− 1) after 100 cycles at 0.5 C rate was obtained for the FeF3-coated Li[Li0.2Mn0.54Ni0.13Co0.13]O2 cathode. Besides, the results from cyclic voltammetry and electrochemical impedance spectra revealed that the noteworthy enhanced electrochemical properties of the surface-modified sample were due to the presence of FeF3 coating layer, which suppressed the side reaction between the Li[Li0.2Mn0.54Ni0.13Co0.13]O2 particles with electrolyte and further stabilized the Li[Li0.2Mn0.54Ni0.13Co0.13]O2 structure with cycling.

Prefabricated construction has attracted research interest as it can significantly improve the energy, cost, and time efficiency of construction. However, dispatching the required prefabricated components to construction sites in a prefabricated system is challenging. To address this issue, we modeled the dispatching problem as a special type of vehicle routing problem with time windows (VRPTW) and solved it by using an improved artificial bee colony (IABC) algorithm. First, to efficiently solve the cross-synchronization problem that occurs in prefabricated systems, two problem-specific lemmas were derived. Then, a hybrid initialization strategy was developed to generate feasible and efficient solutions and a well-designed encoding repair strategy was utilized to make solutions feasible. Finally, a variable length local search strategy was embedded to enhance the exploitation ability. To verify the performance of the proposed IABC algorithm, 55 instances were generated and used for simulation tests. Three efficient algorithms, including the two-phase genetic algorithm (TPGA), improved tabu search algorithm (ITSA), and adaptive large neighborhood search (ALNS) heuristic, were selected for detailed comparisons. Our simulation results show that, considering the energy consumption metric, the proposed algorithm yields average deviations of about 0.099, 0.096, and 0.143 times the values obtained with the TPGA, ITSA, and ALNS heuristic, respectively. The simulation results confirmed that the proposed algorithm can solve the VRPTW in prefabricated systems with high efficiency.

C99 is the immediate precursor of amyloid-β (Aβ) and therefore is a central intermediate in the pathway that is believed to result in Alzheimer's disease (AD). Recent studies have shown that C99 dimerization changes the Aβ ratio, but the mechanism remains unclear. Previous studies of the C99 dimer have produced controversial structure models. To address these questions, we investigated C99 dimerization using molecular dynamics (MD) simulations. A helix-switch model was revealed in the formation and transition of the C99 dimer, and six types of conformations were identified. The different conformations show differential exposures of γ-cleavage sites and insertion depths in the bilayer, which may modulate γ-cleavage of C99 and lead to different Aβ levels. Our results redefine C99 dimerization, provide a framework to mediate the current controversial results, and give insights into the understanding of the relationship between C99 dimerization and Aβ formation.

Beating is the most significant process in papermaking technique that can modify the fiber morphology, sheet-formation ability of fiber suspension and properties of the wet-laid mat. In this paper, flame attenuated glass wool was beaten in water at various revolutions, ranging from 1500r to 12000r. Compared to suspensions beaten at 0r and 1500r where glass fibers simply aggregated in water, glass wool suspensions beaten at 3000r to 8000r were homogeneous with separated and randomly arranged glass fibers. Further, suspensions beaten at revolutions above 8000r were uniform but with a few broken glass fibers. The dewatering characteristics of fiber suspensions were analyzed based on fiber plugging model. Drainage resistances of flame attenuated glass wool suspension increased dramatically from 22 °SR (unbeaten) to 29 °SR (at 1500r) and then maintained at this value till 12000r. Density and porosity of the fabricated wet-laid mat was 95 kg/m 3 and 94%, respectively. Maximum tensile strength of 170 N/m for the wet-laid mat was achieved at 8000r, which then decreased significantly to 100 N/m when the revolutions exceed 10000r.

This paper discussed the effect of various blendings and numbers of beating revolutions on the dewatering properties of hybrid glass wool (HGW) suspensions and tensile strength of the associated glassfiber wet-laid mats. Different percentages of flame attenuated glass wool (FAGW) were blended with centrifuged glass wool (CGW) to form HGW samples. These HGW samples were dispersed in water by beating at various revolutions and each beaten suspension followed the papermaking steps to form subsequent hybrid glassfiber mats (HGM). The suspended solid content, drainage resistance and drainage time of each HGW suspension and pore characteristics and tensile strength of the resulting HGM were recorded. Drainage resistances of all HGW suspensions initially increased with beating revolutions up to 5000r. Afterwards, the drainage resistances fluctuated at different values. The FAGW addition aided the integrity of glass fibers during beating, tuned the microstructure and enhanced the tensile strength of HGM but sacrificed the dewatering efficiency of glass wool suspensions. According to the results from beating revolutions versus tensile strength graph, gentle beating or medium beating benefited the tensile strength of the HGM. The optimum preparation condition for glassfiber wet-laid mats with ideal microstructure, high tensile strength and low manufacturing costs was beating HGW with 30 % CGW and 70 % FAGW at 5000r.

Aluminum cables are playing an increasingly important role in power transmission system, in which the “rare-earth high-iron aluminum alloy power cables were developed in China. In this paper, the effects of B on grain refinement of high-iron aluminum alloy were studied by using OM (optical microscopy), SEM (scanning electron microscopy), EDX (energy dispersive X-Ray spectroscopy) and XRD (X-ray diffraction). And the conductivity of high-iron aluminum alloy was also tested. The results showed that B could take significant effects on grain refinement and promote the increase of conductivity. The refinement may be mainly due to the eutectic reaction in solidification process and the formation of AlB2 particles. The optimal concentration of B was determined as 0.06 wt. %.

It is generally believed that the etiology of Alzheimer's disease (AD) is closely related to the amyloid-β polypeptides, produced from γ-secretase cleavage of C99. There is preliminary evidence that cholesterol directly activates γ-secretase cleavage of C99 through mechanisms that have not been understood so far. In this article, coarse-grained (CG) and all-atom (AT) simulations were employed to investigate the association between C99 and cholesterol, which is essential for our understanding of the role of cholesterol in the amyloidogenic pathway. Firstly, we find that both the N-terminus and the C-terminus of the C99 transmembrane domain (TMD) show interactions with cholesterol. Secondly, a multi-site dynamic cholesterol binding model was captured from the simulations, where 6 binding sites in the C99 TMD were presented. The analyses of the binding energies show that cholesterol prefers the site no. 1, 2, 4 and 5 over others. The most favorable binding energy of nearly −58.857 kJ mol−1 is from site 1, the repeat GxxxG motif. There are two pathways and two binding states of cholesterol binding to this site. Ser697 and Phe690 contribute most to the stabilization of the tightly binding state and the loosely binding state, respectively. The other binding sites described may also be potential drug targets. Thirdly, the residues GAVILMTKF, especially IVKF play a key role in this association. The C99 model appears to suggest a new mechanism for cholesterol binding. Finally, the multiple-site dynamic cholesterol binding model better explains the hypotheses that cholesterol promotes the amyloidogenic AβPP route. The GxxxA motif in the middle of the C99 transmembrane domain is completely exposed without cholesterol sheltering, which might help γ-secretase identify the cleavage sites and then promote γ-cleavage. Our results provide a detailed picture of dynamic cholesterol binding, which is crucial to our recognition of the potential influence of cholesterol on the C99 process and the etiology of AD.

The linguistic dynamic systems (LDSs) based on type-1 fuzzy sets can provide a powerful tool for modeling, analysis, evaluation and control of complex systems. However, as pointed out in earlier studies, it is much more reasonable to take type-2 fuzzy sets to model the existing uncertainties of linguistic words. In this paper, the LDS based on type-2 fuzzy sets is studied, and its reasoning process is realized through the perceptual reasoning method. The properties of the perceptual reasoning method based LDS (PR-LDS) are explored. These properties demonstrated that the output of PR-LDS is intuitive and the computation complexity can be reduced when the consequent type-2 fuzzy numbers in the rule base satisfy some conditions. Further, a data driven method for the design of the PR-LDS is provided. At last, the effectiveness and rationality of the proposed data-driven method are verified by an example.

Vacuum insulation panels (VIPs) are regarded as one of the most promising high-performance thermal insulation solutions on the market today. In this paper, a novel structure, i.e., honeycomb glassfiber mat was proposed as the core material of VIP. The honeycomb glassfiber mat was composed of glass wool mat and glassfiber chopped strand mat. Among them, 70% centrifugal glass wool and 30% flame attenuated glass wool were mixed together to form the 0.5mm-thickness glass wool mat, while thirteen holes with diameter of 10mm were opened uniformly on the surface of glassfiber chopped strand mat. Glassfiber VIPs possessed honeycomb core material have superior thermal conductivity of 1.52mW/(m•K). In order to obtain better thermal insulation performance, ultrafine and stiff fibers with three-dimensional overlapping structure is preferable. Meanwhile, hollow fibers with bifurcated structure are the guarantee of high-strength core material.

To increase the industrial applicability of hypereutectic Al-Si alloys, various methods have been used to refine primary silicon. The addition and refinement effects of phosphorus (P), rare earth metals (RE) on primary Si have been studied widely, But they have been testified be with some disadvantages, that is, the pollution to the environment of P and the high cost of RE, etc. Now, a new refiner - ZnS and the corresponding processing technology were researched. Microstructures of hypereutectic Al-Si alloy (Si wt. 24%) with fine primary Si were successfully obtained. And the primary Si can be refined from more than 80μm to 20μm. And the distribution of primary silicon is getting more uniform.

Vacuum insulation panels (VIPs) are regarded as one of the most promising high performance thermal insulation solutions on the market today. The insulation performance of VIPs mainly depends on the quality of core materials. This paper compared three types of core materials, namely foam insulation material, powder insulation material and fibrous insulation material. Novel structure of core materials which is fiber pore structures packed with different size powder particles is also put forward on this paper. The aim of this paper is to investigate and compare various properties, requirements and possibilities for traditional core materials and put forward possible future core materials of VIPs.

The insulation material VIP in building offers a new material for highly insulated constructions with just a fraction of the required insulation thickness compared to conventional thermal insulation materials. A VIP is basically composed of the core material, the barrier film and getters. Core materials of VIP are glass fiber, fumed silica, fiber-powder composite core. The barrier film covered by glass fiber textile is the protection of the envelope against surface damage and fire attack. We introduce the VIP elements, the system of VIPs in building application and external thermal insulation system with VIP.

Glass wool mat is widely used in the fields of building engineering, transport facilities and refrigeration equipment. In this paper, the effect of material parameters such as density, thickness, porosity, and flow resistivity on the normal incidence absorption coefficient has been studied. In addition, fiber length is also investigated to achieve appropriate strength. The prediction error of normal incidence absorption coefficient by modified Johnson–Allard model is less than 5% in the frequency range between 800 Hz and 5 kHz. We could use the modified Johnson–Allard model to determine the parameter of glass wool mat for better development.

An energy-saving control system for building heating supply system is presented in this paper. Its design and implementation are on the basis of occupancy detection in buildings. By taking advantage of the information fusion technology, the control system will determine human’s location and control the heating equipments automatically according to non-human zone and human zone to realize the energy saving. The information fusion technology fuses three categories of information, which are the people counting information, the infrared sensors information and the RFID information. How to design and implement the heating energy-saving control system is described explicitly in this paper. Since the system has developed with platform concept based on the wireless network and the Internet, it can be used to other building electrical equipment systems with less modification.

Magnesium oxychloride cement sawdust concrete box caused great harm to the environment. This article introduced the method to recycle the box. Magnesium oxychloride cement sawdust concrete was gradually heated, in the range of 0 ~ 800°C, and then the residue was calcined at 700 ° C. Studies showed that the 5•1•8 and sawdust in the box was decomposed into MgO in high temperature conditions. The X-ray diffraction examination results showed that the content of this MgO reached 90%. The application the MgO is very wide.

The level adjustment of cable-driven parallel mechanism is challenging due to the difficulty in obtaining an accurate mathematical model and the fact that different sources of uncertainties exist in the adjustment process. This paper presents a type-2 fuzzy neural network (T2FNN) based inverse control scheme for the level adjustment process. The T2FNN, whose consequent interval weights are trained by the iterative least squares estimation method, is used to approximate the inverse dynamics of the process and to handle uncertainties. Finally, the proposed control scheme and its counterpart — type-1 fuzzy neural network based inverse control scheme — are compared and implemented for leveling the cable-driven parallel mechanism.

The DAP12-NKG2C activating immunoreceptor complex is one of the multisubunit transmembrane protein complexes in which ligand-binding receptor chains assemble with dimeric signal-transducing modules through non-covalent associations in their transmembrane (TM) domains. In this work, both coarse grained and atomistic molecular dynamic simulation methods were applied to investigate the self-assembly dynamics of the transmembrane domains of the DAP12-NKG2C activating immunoreceptor complex. Through simulating the dynamics of DAP12-NKG2C TM heterotrimer and point mutations, we demonstrated that a five-polar-residue motif including: 2 Asps and 2 Thrs in DAP12 dimer, as well as 1 Lys in NKG2C TM plays an important role in the assembly structure of the DAP12-NKG2C TM heterotrimer. Furthermore, we provided clear evidences to exclude the possibility that another NKG2C could stably associate with the DAP12-NKG2C heterotrimer. Based on the simulation results, we proposed a revised model for the self-assembly of DAP12-NKG2C activating immunoreceptor complex, along with a plausible explanation for the association of only one NKG2C with a DAP12 dimer.

It is commonly believed that the IPv6 provides greater security against worms by its huge address space. We show that a P2P-based worm can exploit the P2P services to spread in the IPv6 Internet. The P2P-based worm applies a two-phase scanning mechanism to find targets. The behavior of such a worm in this paper is modeled. We explore via analysis and simulation the spread of such worms in an IPv6 Internet. Our results indicate that such a worm can exhibit propagation speeds comparable to an IPv4 random-scanning worm. We develop a detailed analytical model that reveals the relationship between network parameters and the spreading rate of the worm in an IPv6 world. It is also noted that the P2P-based worm may influence the propagation of the worm in the Internet.