Capacity Of Arc Research Articles

Endogenous capsid-forming protein ARC for self-assembling nanoparticle vaccines

The application of nanoscale scaffolds has become a promising strategy in vaccine design, with protein-based nanoparticles offering desirable avenues for the biocompatible and efficient delivery of antigens. Here, we presented a novel endogenous capsid-forming protein, activated-regulated cytoskeleton-associated protein (ARC), which could be engineered through the plug-and-play strategy (SpyCatcher3/SpyTag3) for multivalent display of antigens. Combined with the self-assembly capacity and flexible modularity of ARC, ARC-based vaccines elicited robust immune responses against Mpox or SARS-CoV-2, comparable to those induced by ferritin-based vaccines. Additionally, ARC-based nanoparticles functioned as immunostimulants, efficiently stimulating dendritic cells and facilitating germinal center responses. Even without adjuvants, ARC-based vaccines generated protective immune responses in a lethal challenge model. Hence, this study showed the feasibility of ARC as a novel protein-based nanocarrier for multivalent surface display of pathogenic antigens and demonstrated the potential of exploiting recombinant mammalian retrovirus-like protein as a delivery vehicle for bioactive molecules.Graphic

Arc ubiquitination regulates endoplasmic reticulum-mediated Ca2+ release and CaMKII signaling.

Synaptic plasticity relies on rapid, yet spatially precise signaling to alter synaptic strength. Arc is a brain enriched protein that is rapidly expressed during learning-related behaviors and is essential for regulating metabotropic glutamate receptor-mediated long-term depression (mGluR-LTD). We previously showed that disrupting the ubiquitination capacity of Arc enhances mGluR-LTD; however, the consequences of Arc ubiquitination on other mGluR-mediated signaling events is poorly characterized. Here we find that pharmacological activation of Group I mGluRs with S-3,5-dihydroxyphenylglycine (DHPG) increases Ca2+ release from the endoplasmic reticulum (ER). Disrupting Arc ubiquitination on key amino acid residues enhances DHPG-induced ER-mediated Ca2+ release. These alterations were observed in all neuronal subregions except secondary branchpoints. Deficits in Arc ubiquitination altered Arc self-assembly and enhanced its interaction with calcium/calmodulin-dependent protein kinase IIb (CaMKIIb) and constitutively active forms of CaMKII in HEK293 cells. Colocalization of Arc and CaMKII was altered in cultured hippocampal neurons, with the notable exception of secondary branchpoints. Finally, disruptions in Arc ubiquitination were found to increase Arc interaction with the integral ER protein Calnexin. These results suggest a previously unknown role for Arc ubiquitination in the fine tuning of ER-mediated Ca2+ signaling that may support mGluR-LTD, which in turn, may regulate CaMKII and its interactions with Arc.

Improvement of fatigue strength in heavy steel constructions through arc brazing

AbstractThe possibility of arc brazing of non‐loaded attachments with the filler material CuAl7 instead of welding on cyclically stressed steel constructions was investigated. The notch effect under cyclic loading was significantly reduced for non‐loaded arc brazed plates on base material of S355 and therefore the fatigue strength improved. The specimens did not show sensitivity to changes of the thickness and size of the non‐loaded arc brazed plates during fatigue testing. Furthermore, no negative thickness effect by increasing the thickness of the base material was observed. Microstructural analysis showed that the dimension of the heat affected zone was reduced through reduced heat input and that liquid metal penetration (LMP) occurs in the base metal, which has no negative effect on fatigue strength. Measurements of residual stresses in the weld / braze toe area showed that tensile residual stresses have not significantly been reduced, which can be attributed to comparable reactional forces of the copper alloy during cooling through a higher coefficient of thermal expansion. Numerical analysis showed that compared to a welded detail, the stress concentrations on the weld toe of the arc brazed fillets drop significantly due to the lower Young's Modulus of the alloy. The static testing of the load bearing capacity of arc brazed attachments showed that high tensile and shear stresses, which are comparable to the strength of the base metal, can be reached before fracture.

Capability enhancement of production of activating fluxes for arc welding using ultradispersed products of silicon waste processing

Experimental results on welding with the help of activating flux are presented. It includes nanosilica obtained from metallurgical wastes. As a result of the use of the developed composition of the activating flux, melting capacity of the welding arc increased by 1.5-3 times, energy intensity of the process decreased by 30-50%.

Lung tumor promotion by chromium-containing welding particulate matter in a mouse model

BackgroundEpidemiology suggests that occupational exposure to welding particulate matter (PM) may increase lung cancer risk. However, animal studies are lacking to conclusively link welding with an increased risk. PM derived from stainless steel (SS) welding contains carcinogenic metals such as hexavalent chromium and nickel. We hypothesized that welding PM may act as a tumor promoter and increase lung tumor multiplicity in vivo. Therefore, the capacity of chromium-containing gas metal arc (GMA)-SS welding PM to promote lung tumors was evaluated using a two-stage (initiation-promotion) model in lung tumor susceptible A/J mice.MethodsMale mice (n = 28-30/group) were treated either with the initiator 3-methylcholanthrene (MCA;10 μg/g; IP) or vehicle (corn oil) followed by 5 weekly pharyngeal aspirations of GMA-SS (340 or 680 μg/exposure) or PBS. Lung tumors were enumerated at 30 weeks post-initiation.ResultsMCA initiation followed by GMA-SS welding PM exposure promoted tumor multiplicity in both the low (12.1 ± 1.5 tumors/mouse) and high (14.0 ± 1.8 tumors/mouse) exposure groups significantly above MCA/sham (4.77 ± 0.7 tumors/mouse; p = 0.0001). Multiplicity was also highly significant (p < 0.004) across all individual lung regions of GMA-SS-exposed mice. No exposure effects were found in the corn oil groups at 30 weeks. Histopathology confirmed the gross findings and revealed increased inflammation and a greater number of malignant lesions in the MCA/welding PM-exposed groups.ConclusionsGMA-SS welding PM acts as a lung tumor promoter in vivo. Thus, this study provides animal evidence to support the epidemiological data that show welders have an increased lung cancer risk.

M Cells Prefer Archaeosomes: An In Vitro/In Vivo Snapshot Upon Oral Gavage in Rats

The archaeolipids (lipids extracted from archaebacterias) are non saponificable molecules that form self sealed mono or bilayers (archaeosomes-ARC). Different to liposomes with bilayers made of conventional glycerophospholipids, the bilayer of ARC posses a higher structural resistance to physico chemical and enzymatic degradation and surface hydrophobicity. In this work we have compared the binding capacity of ARC exclusively made of archaeols containing a minor fraction of sulphoglycophospholipids, with that of liposomes in gel phase on M-like cells in vitro. The biodistribution of the radiopharmaceutical (99m)Tc-DTPA loaded in ARC vs that of liposomes upon oral administration to Wistar rats was also determined. The fluorescence of M-like cells upon 1 and 2h incubation with ARC loaded with the hydrophobic dye Rhodamine-PE (Rh-PE) and the hydrophilic dye pyranine (HPTS) dissolved in the aqueous space, was 4 folds higher than upon incubation with equally labeled liposomes. Besides, 15% of Rh-PE and 13 % of HPTS from ARC and not from liposomes, were found in the bottom wells, a place that is equivalent to the basolateral pocket from M cells. This fact suggested the occurrence of transcytosis of ARC. Finally, 4 h upon oral administration, ARC were responsible for the 22.3 % (3.5 folds higher than liposomes) shuttling of (99m)Tc-DTPA to the blood circulation. This important amount of radioactive marker in blood could be a consequence of an extensive uptake of ARC by M cells in vivo, probably favored by their surface hydrophobicity. Taken together, these results suggested that ARC, proven their adjuvant capacity when administered by parenteral route and high biocompatibility, could be a suitable new type of nanoparticulate material that could be used as adjuvants by the oral route.

ON THE BOTTLENECK CAPACITY EXPANSION PROBLEMS ON NETWORKS

This article considers a class of bottleneck capacity expansion problems. Such problems aim to enhance bottleneck capacity to a certain level with minimum cost. Given a network G( V, A, ▪) consisting of a set of nodes V = { v 1, v 2, ⋯, v n }, a set of arcs A ⊆ {( v i, v j ) | i = 1, 2, ⋯, n; j = 1, 2, ⋯, n} and a capacity vector ▪. The component ▪ of ▪ is the capacity of arc ( v i, v j ). Define the capacity of a subset A' of A as the minimum capacity of the arcs in A, the capacity of a family F of subsets of A is the maximum capacity of its members. There are two types of expanding models. In the arc-expanding model, the unit cost to increase the capacity of arc ( v i, v j ) is w ij. In the node-expanding model, it is assumed that the capacities of all arcs ( v i, v j ) which start at the same node v i should be increased by the same amount and that the unit cost to make such expansion is w i . This article considers three kinds of bottleneck capacity expansion problems (path, spanning arborescence and maximum flow) in both expanding models. For each kind of expansion problems, this article discusses the characteristics of the problems and presents several results on the complexity of the problems.

OPTIMAL ROUTING WITH CAPACITY, RELIABILITY AND COST CONSTRAINTS

This paper considers a graph G in a network in which each arc (i,j) is weighted with a vector (kij, pij, cij) where kij is the capacity of arc (i,j), pi,j is its reliability and ci,j is the cost associated with traversing the arc (i,j). The problem is to find the route from source to sink with maximum capacity, within a threshold reliability R and at a total cost of no more than C. This problem has a particular type of Pareto optimal solution and is distinct from the problem discussed by Sancho5 in which all Pareto optimal solutions are found. In theory, many Pareto optimal solutions can exist; hence the need for finding a method in which the particular optimal solution can be found. The application of transporting hazardous material is an example of this particular problem.

On the Maximum Expected Flow in a Network

Consider a graph G in which every arc (i, j) has two numbers, ρij and cij, associated with it representing the reliability and capacity of the arc respectively. It is shown that the expected flow is equal to the sum of the expected capacities of the paths from source to sink. An algorithm is described to find the maximum expected flow in the network.

Reliability Evaluation of Flow Networks Using Delta-Star Transformations

A new approach based on delta-star and/or star-delta transformations is presented for calculating the maximum network flow between a pair of nodes. The procedure consists of simplifying complex structures by converting them into equivalent series parallel configurations and successively reducing the network until a single arc in obtained. The capacity of the single arc is the maximum flow between the pair of nodes. Given the pmf's of the network arcs, the pmf of the maximum flow can be obtained using these transformations. The system reliability can be determined from this pmf.