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The results of studies on the production of welding wires with a diameter of 2.5 and 3.3 mm from alloy 1580 are presented. To compare the manufacturability of the processing, various methods were used to obtain billets for drawing with a diameter of 8-12 mm: the traditional method of direct hot extruding (discrete); combined rolling-extruding method; and ingotless rolling-extruding method (continuous). The developed modes of bar rolling, drawing and annealing made it possible to obtain prototypes of wire in laboratory and industrial conditions. It was found that alloy 1580 is highly manufacturable both with the traditional method of pressure treatment (extruding) and with combined rolling-extruding methods. It was revealed that the application of all methods makes it possible to obtain billets with the level of mechanical properties necessary for further multi-operation processing. Based on the results of research obtained in laboratory conditions, rational drawing modes for industrial wire production have been developed. As a result of bay drawing, pilot batches of welding wire with a diameter of 3.26 and 2.47 mm from alloy 1580 were obtained, which was successfully used for welding sheet metal.

The results of computer simulation of the process of combined rolling-extruding of longish deformed semi-finished products from alloy 01417 are presented. A feature of the research is that continuously cast bars with a diameter of 12.5 mm obtained using an electromagnetic mold are used as a workpiece. This makes it possible to increase the manufacturability of processing and to obtain after rolling-extruding billets for drawing with a diameter of 5 mm with a large resource of plastic and strength properties. For this case the technological parameters and temperature and speed conditions of combined processing have not yet been studied, therefore, their analysis was performed using the Deform-3D software package. It has been revealed that the feasibility of the rolling-extruding process is significantly affected by the frequency of rotation of the rolls. Moreover, the process becomes unstable when the value of this parameter is 4 rpm, which can be explained by insufficient degrees of deformation during rolling, and consequently by the small value of the active friction forces acting on the contact surface of the metal with the rolls. As a result of this, the processing temperature conditions also change, which is also demonstrated using the developed computer model. As a result, it was found that for the stable course of the combined rolling-extruding process at the CRE-200 unit of a continuously cast billet with a diameter of 12.5 mm from alloy 01417 at a heating temperature of the billet of 550 °C and a tool of 200 °C, degree of deformation during rolling 44% and drawing ratio during extruding 18.6 the frequency of rotation of the rolls should be at least 8 rpm. The simulation data used during the implementation of the process at the combined processing unit CRE-200, the results of which made it possible to finally obtain electrotechnical wire with a diameter of 0.5 mm from 01417 alloy that meets the requirements of TS 1-809-63-2018.

The article presents the results of studies on the production of wire with a diameter of 0.5 mm from aluminum alloy 01417 with a content of rare-earth metals (REM) in the amount of 7-9% for aircraft construction needs. The deformation modes, the experimental technique and equipment for the implementation of the proposed technology described. The wire was obtained by drawing and bar rolling with subsequent drawing from a rod with a diameter of 5 mm, obtained previously using the process of combined rolling-extruding (CRE) from a continuous ingot with a diameter of 12 mm, cast in an electromagnetic mold (EMM). The wire obtained by the presented technology was subjected to 4 different heat treatment modes with annealing temperatures from 350 to 500 °C and holding time of 1 h in the furnace to achieve mechanical and electrophysical properties corresponding to TS 1-809-1038-2018. The level of strength and plastic properties obtained in the course of research required only one intermediate annealing. The microstructure of the wire was investigated and the modes were revealed that made it possible to obtain the required level of mechanical properties and electrical resistivity, satisfying TS 1-809-1038-2018.

Salmonella enterica is an intracellular bacterial pathogen that resides and proliferates within a membrane-bound vacuole in epithelial cells of the gut and gallbladder. Although essential to disease, how Salmonella escapes from its intracellular niche and spreads to secondary cells within the same host, or to a new host, is not known. Here, we demonstrate that a subpopulation of Salmonella hyperreplicating in the cytosol of epithelial cells serves as a reservoir for dissemination. These bacteria are transcriptionally distinct from intravacuolar Salmonella. They are induced for the invasion-associated type III secretion system and possess flagella; hence, they are primed for invasion. Epithelial cells laden with these cytosolic bacteria are extruded out of the monolayer, releasing invasion-primed and -competent Salmonella into the lumen. This extrusion mechanism is morphologically similar to the process of cell shedding required for turnover of the intestinal epithelium. In contrast to the homeostatic mechanism, however, bacterial-induced extrusion is accompanied by an inflammatory cell death characterized by caspase-1 activation and the apical release of IL-18, an important cytokine regulator of gut inflammation. Although epithelial extrusion is obviously beneficial to Salmonella for completion of its life cycle, it also provides a mechanistic explanation for the mucosal inflammation that is triggered during Salmonella infection of the gastrointestinal and biliary tracts.

With an increasing incidence of orthopedic fractures due to the growing aging population, the demand for novel bone tissue engineering treatments is rising. Existing biopolymeric scaffolds have hierarchical structure, are biocompatible, and are biodegradable, but struggle to control pore size and interconnectivity, essential features to regulate cell alignment and mechanobiological signaling. This highlights the need to design a biopolymeric scaffold with well-defined hierarchical structure and optimized surface properties to improve bone regeneration. To accomplish this, we proposed a grid-in-grid manufacturing approach and fabricated a solvent-free 3D polycaprolactone (PCL) scaffold with hierarchical pores using precision extruding deposition (PED) 3D printing technology. The fabricated scaffolds exhibit both global pores and multi-scale local pores. Notably, using in vitro cultured human mesenchymal stem cells (hMSCs), controlled local pore size induced contact guidance and pore bridging, and the surface roughness of global strands effectively led to cell alignment. This study demonstrates that precision 3D printing technology can directly manipulate local pore structures to control cell migration and alignment. Furthermore, it could be applied for combined bone to connective tissue regeneration, where gradient pore structures and cell alignment are essential. Our scaffold has the potential to serve as a customizable platform for advanced tissue engineering applications.

Heavy-metal homeostasis and detoxification is crucial for cell viability. P-type ATPases of the class IB (PIB) are essential in these processes, actively extruding heavy metals from the cytoplasm of cells. Here we present the structure of a PIB-ATPase, a Legionella pneumophila CopA Cu + -ATPase, in a copper-free form, as determined by X-ray crystallography at 3.2 Å resolution. The structure indicates a three-stage copper transport pathway involving several conserved residues. A PIB-specific transmembrane helix kinks at a double-glycine motif displaying an amphipathic helix that lines a putative copper entry point at the intracellular interface. Comparisons to Ca 2+ -ATPase suggest an ATPase-coupled copper release mechanism from the binding sites in the membrane via an extracellular exit site. The structure also provides a framework to analyse missense mutations in the human ATP7A and ATP7B proteins associated with Menkes’ and Wilson’s diseases. Copper transport dissected Class IB P-type ATPases perform an important cellular function by regulating the levels of heavy metals, copper in particular, thus providing protein cofactors and maintaining appropriate intracellular concentrations to prevent toxic reactions. In humans, defects in two proteins of this class (the copper pumps ATP7A and ATP7B) give rise to the severe Menkes' and Wilson's diseases. The X-ray crystal structure of a class IB P-type Cu+-ATPase has now been determined in its copper-free state. The structure of CopA from Legionella pneumophila suggests that the copper-transport pathway has three main stages: a cytoplasmic 'entry' site, binding sites in the membrane and an extracellular 'exit' site.

The three-dimensional (3D) printing technique for cement-based materials has been actively investigated and utilized in civil engineering. However, there is no systematic review of the fabricating devices. This paper reviews the software and hardware for extrusion-based 3D concrete printing. Firstly, a dedicated tool path generating software is urgently needed to meet the cementitious printing applications and to improve printing quality with toolpath optimizations. Secondly, the existing printing equipment was summarized and discussed, concluding the pros and cons of various 3D motion systems, material systems, and nozzle units. Suitable choices for scientific research and engineering applications were recommended. The reinforcing techniques were categorized and concluded with the existing drawbacks and the research trend. A hybrid manufacturing system of 3D printing and the reinforcing technique was then proposed with a system diagram and flowchart.

Rivaroxaban (RXB), a novel oral anticoagulant that directly inhibits factor Xa, is a poorly soluble drug belonging to Biopharmaceutics Classification System (BCS) class II. In this study, a hot-melt extruded amorphous solid dispersion (HME-ASD) containing RXB is prepared by changing the drug:polymer ratio (Polyvinylpyrrolidione-vinyl acetate 64, 1:1–1:4) and barrel temperature (200–240 °C), fixed at 20% of Cremophor® RH 40 and 15 rpm of the screw speed, using the hot-melt extruding technique. This study evaluates the solubility, dissolution behavior, and bioavailability for application to oral drug delivery and optimizes the formulation of rivaroxaban amorphous solid dispersion (RXB-ASD). Based on a central composite design, optimized RXB-ASD (PVP VA 64 ratio 1:4.1, barrel temperature 216.1 °C, Cremophor® RH 40 20%, screw speed 15 rpm) showed satisfactory results for dependent variables. An in vitro drug dissolution study exhibited relatively high dissolution in four media and achieved around an 80% cumulative drug release in 120 min. Optimized RXB-ASD was stable under the accelerated condition for three months without a change in crystallinity and the dissolution rate. A pharmacokinetic study of RXB-ASD in rats showed that the absorption was markedly increased in terms of rate and amount, i.e., the systemic exposure values, compared to raw RXB powder. These results showed the application of quality by design (QbD) in the formulation development of hot-melt extruded RXB-ASD, which can be used as an oral drug delivery system by increasing the dissolution rate and bioavailability.

The paper presents the results of studies of the structure and properties of a wire with a diameter of 0.5 mm from an alloy of the Al-REM system with a rare-earth metal content of 7–9%. Wire obtained as a result of the implementation of the technology of its manufacture using the methods of casting into an electromagnetic mold (EMM), continuous extruding, and drawing. The rheological properties of the metal of continuously cast round billets from the experimental alloy obtained using an electromagnetic mold are determined. The modeling and analytical assessment of the possibility of carrying out the process of combined rolling-extruding (CRE) of such billets in a closed box-type roll groove of a continuous extruding unit are carried out. The features of metal shaping have been studied. The temperature-speed and technological parameters were found at which the CRE process can be carried out in a stable mode of operation. Data have been obtained for the forces acting on the die and rolls during rolling-extruding. The results of experimental studies of the process of obtaining longish deformed semi-finished products from an experimental alloy on the laboratory unit CRE-200 and the pilot plant unit CRE-400 are presented. The structure of the metal has been studied; data on the ultimate tensile strength, yield strength, relative elongation, and electrical resistance of hot-extruded rods and wires in cold-worked and annealed states have been obtained. It was found that the proposed processing modes make it possible to obtain by the method of combined rolling-extruding rods with a diameter of 9 mm in industrial conditions from longish billets with a diameter of 18 mm, cast by means of EMM. Wire in a cold-deformed and annealed state with a diameter of 0.5 obtained by drawing from the rods with a diameter of 9 mm from an experimental alloy of the Al-REM system containing 7–9% rare-earth metals with the required physical and mechanical properties.

Newly developed active pharmaceutical ingredients (APIs) are often poorly soluble in water. As a result the bioavailability of the API in the human body is reduced. One approach to overcome this restriction is the formulation of amorphous solid dispersions (ASDs), e.g., by hot-melt extrusion (HME). Thus, the poorly soluble crystalline form of the API is transferred into a more soluble amorphous form. To reach this aim in HME, the APIs are embedded in a polymer matrix. The resulting amorphous solid dispersions may contain small amounts of residual crystallinity and have the tendency to recrystallize. For the controlled release of the API in the final drug product the amount of crystallinity has to be known. This review assesses the available analytical methods that have been recently used for the characterization of ASDs and the quantification of crystalline API content. Well-established techniques like near- and mid-infrared spectroscopy (NIR and MIR, respectively), Raman spectroscopy, and emerging ones like UV/VIS, terahertz, and ultrasonic spectroscopy are considered in detail. Furthermore, their advantages and limitations are discussed with regard to general practical applicability as process analytical technology (PAT) tools in industrial manufacturing. The review focuses on spectroscopic methods which have been proven as most suitable for in-line and on-line process analytics. Further aspects are spectroscopic techniques that have been or could be integrated into an extruder.