SEARCH · Engineering Papers

Results for “insertion”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,117 records · Page 62

All sources NASA NTRS DOE OSTI

DOE OSTI2020

Actinide and rare earth drawdown system for molten salt recycle

A method for recycling molten salt from electrorefining processes, the method having the steps of collecting actinide metal using a first plurality of cathodes from an electrolyte bath, collecting rare earths metal using a second plurality of cathodes from the electrolyte bath, inserting the collected actinide metal and uranium into the bath, and chlorinating the inserted actinide metal and uranium. Also provided is a system for recycling molten salt, the system having a vessel adapted to receive and heat electrolyte salt, a first plurality of cathodes adapted to be removably inserted into the vessel, a second plurality of cathodes adapted to be removably inserted into the vessel, an anode positioned within the vessel so as to be coaxially aligned with the vessel, and a vehicle for inserting uranium into the salt.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

DOE OSTI2021

Closed impeller with self-recirculation casing treatment

A closed impeller includes: a housing provided with an opening; an insert inserted into one side of the opening; and an impeller body inserted into the other side of the opening, and including a plurality of blades and a shroud covering the plurality of blades, wherein the insert is provided with an inflow channel guiding a fluid into an inlet of the impeller body, and wherein a clearance between an outer surface of the insert and an inner surface of the housing forms a circulation flow channel connecting the other end of the inflow channel with a portion where one end of the inflow channel meets the inlet of the impeller body.

Pelton, Robert Young↗

DOE OSTI2023

Actinide and rare earth drawdown system for molten salt recycle

Willit, James L.↗

DOE OSTI2024

Heat Transfer Experiments of Ribbed, Serpentine Cooling Passages with Supercritical CO2

The results of heat transfer experiments with supercritical CO2 (sCO2) to capture the performance of ribbed, serpentine cooling passages for Reynolds numbers in the range of 100,000 - 400,000 are presented. The oxy-combustion turbine operating in an Allam-Fetvedt cycle has a turbine inlet temperature exceeding 1100°C, necessitating internally cooled turbine blades due to material creep strength limits. Reynolds numbers for sCO2, with its combination of high fluid density and low viscosity, can be up to an order of magnitude higher than comparable internal cooling conditions for an air-breathing engine where the majority of experimental data exists. To improve the prediction of cooling performance through turbulated passages, a test rig was designed and constructed with interchangeable insert capability for operation in sCO2 with heat transfer from a heater outlet flow stream to a lower temperature recuperator outlet flow stream. The inserts included serpentine passage geometry with five passes, one of the inserts including chevron ribs and the other a plain wall. The multi-pass serpentine geometry allowed for the evaluation of the effects 180 deg. tip turns have on the return passage flow characteristics, as they can depart significantly from fully-developed flow characteristics. The test procedure included the use of a modified Wilson plot method, with hot flow stream conditions kept effectively constant so that monitored changes in the overall thermal resistance could be attributed to manipulations in cooling flow stream conditions. Conditions during testing consisted of test section pressures of approximately 180 bar, cooling flow stream temperature of 175°C and hot flow stream temperature of 410°C. Test points at discrete cool flow Reynolds numbers up to 400,000 demonstrated an expected trend of decreased fluid thermal resistance with increasing Reynolds number, while at comparable Reynolds number there was an exhibited lower thermal resistance and higher passage pressure drop for the ribbed insert compared to the plain-walled insert. Processing of test data included establishment of Nusselt number enhancement ratios, so that for different internal cooling passage dimensions in the actual turbine blade at comparable Reynolds number the ratio could be applied to predict cooling performance.

Marshall, Michael↗

DOE OSTI2022

Electroactive ZnO: Mechanisms, Conductivity, and Advances in Zn Alkaline Battery Cycling

Zinc oxide is of great interest for advanced energy devices because of its low cost, wide direct bandgap, non-toxicity, and facile electrochemistry. In zinc alkaline batteries, ZnO plays a critical role in electrode passivation, a process that hinders commercialization and remains poorly understood. Here, novel observations of an electroactive type of ZnO formed in Zn-metal alkaline electrodes are disclosed. The electrical conductivity of battery-formed ZnO is measured and found to vary by factors of up to 10 4 , which provides a first-principles-based understanding of Zn passivation in industrial alkaline batteries. Simultaneous with this conductivity change, protons are inserted into the crystal structure and electrons are inserted into the conduction band in quantities up to ≈10 20 cm –3 and ≈1 mAh gZnO –1 . Electron insertion causes blue electrochromic coloration with efficiencies and rates competitive with leading electrochromic materials. The electroactivity of ZnO is evidently enabled by rapid crystal growth, which forms defects that complex with inserted cations, charge-balanced by the increase of conduction band electrons. Furthermore, this property distinguishes electroactive ZnO from inactive classical ZnO. Knowledge of this phenomenon is applied to improve cycling performance of industrial-design electrodes at 50% zinc utilization and the authors propose other uses for ZnO such as electrochromic devices.

36 MATERIALS SCIENCE↗

DOE OSTI2012

Ribonuclease A suggests how proteins self-chaperone against amyloid fiber formation

Genomic analyses have identified segments with high fiber-forming propensity in many proteins not known to form amyloid. Proteins are often protected from entering the amyloid state by molecular chaperones that permit them to fold in isolation from identical molecules; but, how do proteins self-chaperone their folding in the absence of chaperones? Here, we explore this question with the stable protein ribonuclease A (RNase A). We previously identified fiber-forming segments of amyloid-related proteins and demonstrated that insertion of these segments into the C-terminal hinge loop of nonfiber-forming RNase A can convert RNase A into the amyloid state through three-dimensional domain-swapping, where the inserted fiber-forming segments interact to create a steric zipper spine. In this study, we convert RNase A into amyloid-like fibers by increasing the loop length and hence conformational freedom of an endogenous fiber-forming segment, SSTSAASS, in the N-terminal hinge loop. This is accomplished by sandwiching SSTSAASS between inserted Gly residues. With these inserts, SSTSAASS is now able to form the steric zipper spine, allowing RNase A to form amyloid-like fibers. We show that these fibers contain RNase A molecules retaining their enzymatic activity and therefore native-like structure. Thus, RNase A appears to prevent fiber formation by limiting the conformational freedom of this fiber-forming segment from entering a steric zipper. Our observations suggest that proteins have evolved to self-chaperone by using similar protective mechanisms.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2019

Development of Repeatable Microcatheter Access Port for Intra-arterial Therapy of Liver Cancer

Purpose: To develop an implantable port in which a microcatheter can be inserted for a combination therapy of repeated transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) for advanced liver cancer. Materials and Methods: The design of a currently used implantable port was modified. A funnel part was constructed in the port. The septum was punctured by a 20-gauge indwelling needle, and 2.0-Fr non-tapered microcatheter was inserted into the port. In the in vitro studies, the advance of a microcatheter out of the funnel part was evaluated via seven different septum puncture sites. A 5-Fr indwelling catheter connected to the port was placed in a vascular model, and a microcatheter catheterization was evaluated. In an in vivo study, the port–catheter system was implanted in the hepatic artery in a pig. A microcatheter was percutaneously inserted through the port into the hepatic arterial branches, and embolization was performed. Results: In the in vitro studies, the microcatheter was smoothly advanced out of the port and catheterizations into the hepatic arteries were successful via all septum puncture sites. In the in vivo study, repeated selective embolization through the port was successfully conducted on 7, 14 and 21 days after the implantation. Conclusion: The developed implantable port can be used for repeated catheter insertion into the hepatic artery. The combination of repeated TACE and HAIC could be possible using this device.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2019

Multiple Bifurcated Covered Self-Expanding Metallic Stents for Complex Tracheobronchial Fistulas or Stenosis

Objective: We aimed to determine the safety and feasibility of bifurcated covered self-expanding stents for the treatment of complex tracheobronchial fistulas or stenosis. Methods: Twenty-eight patients were treated by multiple bifurcated covered airway stents (Micro-Tech Co. Ltd., Nanjing, China), including 18 cases of gastrobronchial or gastrotracheal fistula, 6 cases of bronchopleural fistula and 4 cases of severe tracheobronchial stenosis. The large bifurcated covered stent was placed at the main carina, and the small stents were inserted into primary right carina or secondary left carina. Clinical and imaging data were retrospectively analyzed. Results: Stents were successfully inserted in 27 patients at the first attempt. In total, 29 large bifurcated covered stents, 27 small bifurcated covered stents and 5 small bifurcated covered single-plugged stents were inserted. All patients with fistula could resume eating without coughing after the procedure. No perioperative death or severe complications occurred. Two patients underwent stent removal due to intolerance of stenting; the clinical success rate was 93% (26/28). Nineteen complications were found in 12 patients; 8 patients needed stent removal or replacement, for a major complication rate of 29% (8/28). Eight patients underwent successful stent removal due to complications. Fifteen patients died of tumors and one patient died of pulmonary infection. The median survival was 33 months. Fistula recurrence was found in one patient 5 months after stenting, and second small bifurcated covered stent was inserted. Conclusions: Multiple bifurcated covered metallic stenting is effective and safe for complex tracheobronchial fistulas or stenosis, with good symptom palliation.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2017

Ab initio modeling of transport and thermodynamic stability for hafnia memristive devices

HfO 2 -based memristive switching devices are currently under intensive investigation due to their high performance and mature fabrication techniques. However, several critical issues have to be addressed to bring them from lab to market. We have recently looked into two important issues with the use of density functional theory methods. One is the wide distribution of device resistance in off-states. We have modeled the switching process of a Pt-HfO 2 -Pt structure for which quantized conductance was observed. Oxygen atoms moving inside a conductive oxygen vacancy filament divide the filament into several quantum wells. Device conductance changes exponentially when one oxygen atom moves away from interface into filament. We propose that the high sensitivity of device conductance to the position of oxygen atoms results in the large variation of device off-state resistance. Another issue that we have recently addressed is the poor switching performance of devices based on a TiN-HfO 2 -TiN structure. While recent experiments have shown that by inserting an "oxygen scavenger" metal between positive electrode and oxide significantly improves device performance, the fundamental understanding of the improvement is lacking.We provide detailed understanding how scavenger layers improve device performance. First, we show that Ta insertion facilitates formation of on-states by reducing the formation energy. Second, the inserted Ta layer reduces the Schottky barrier height in the off-states by changing interface electric dipole at the oxide electrode interface. Nevertheless, the device maintains a high on/off resistance ratio. Finally, with Ta insertion the on-state conductance becomes much less sensitive to the specific location from which the oxygen was removed from the oxide. In conclusion, our studies provide fundamental understanding needed for enabling realization of a non-volatile memory technology with reduced energy consumption.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

DOE OSTI2021

Development of a new control rod drive mechanism design for the ISU AGN-201M reactor

The Aerojet General Nucleonics (AGN) model 201-Modified, known as the AGN-201M reactor, plays an essential role in the educational and research activities at Idaho State University (ISU). The ISU AGN-201M's original Control Rod Drive Mechanism (CRDM) has been in operation for more than fifty years with no large-scale redesigns. The CRDM is required to eject the fuel rods within one second during a SCRAM event (also known as a 'reactor trip') and adjust the control rods' insertion speed, and keeps the rod insertion sequence correct. The existing control rod drive mechanisms meet these criteria but experience a few concerns due to aging. Concerns include complex maintenance and costly repairs for old electromechanical components, rod position feedback errors, and the impediment of the plate during a SCRAM due to binding of the lead screws of the existing mechanism. During a binding event, the drive mechanism becomes locked, preventing the control rod's magnetic plate from moving in or out under the reactor's normal and emergency operating conditions. Although, the binding has no effect on the ability of the rod to exit the core during the SCRAM. To counteract the concerns and issues with the current CRDM, a new design has been proposed using newer components and a simplified design. The new design utilizes more advanced electric and mechanical components that are commercially available. The new CRDM system is divided into four main aspects: (1) control rod movement design (motor, lead screw, guide rods), (2) control rod ejection (springs, electromagnet), (3) control rod position and feedback (position transducer, microswitches), and (4) material selection and structural analysis. The new design aims to reduce the overall complexity and probability of failure to improve the reactor's overall reliability. With proper material selection and improved structural design, the new drives are lighter with little to no change in structural integrity. The new control rod drive mechanism eliminates binding scenarios by using a single lead screw and implementing additional guide rods. An advanced linear position sensor and microswitches replace the existing and aging synchro system for accurate rod position feedback resulting in better reactivity control. The new design meets the reactor's operational limits by having an average reactivity insertion of 0.065% Δk/k per second, which corresponds to a total control rod insertion time of 19.23 s, while the control rod's ejection time remains less than one second during a SCRAM event. The new design ensures the reactor's long-term viability for educational and research activities by increasing the reliability and safety of operation for years to come.

21 SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLANTS↗

DOE OSTI2011

The NDUFB6 subunit of the mitochondrial respiratory chain complex I is required for electron transfer activity: A proof of principle study on stable and controlled RNA interference in human cell lines

Highlights: {yields} NDUFB6 is required for activity of mitochondrial complex I in human cell lines. {yields} Lentivirus based RNA interference results in frequent off target insertions. {yields} Flp-In recombinase mediated miRNA insertion allows gene-specific extinction. -- Abstract: Molecular bases of inherited deficiencies of mitochondrial respiratory chain complex I are still unknown in a high proportion of patients. Among 45 subunits making up this large complex, more than half has unknown function(s). Understanding the function of these subunits would contribute to our knowledge on mitochondrial physiology but might also reveal that some of these subunits are not required for the catalytic activity of the complex. A direct consequence of this finding would be the reduction of the number of candidate genes to be sequenced in patients with decreased complex I activity. In this study, we tested two different methods to stably extinct complex I subunits in cultured cells. We first found that lentivirus-mediated shRNA expression frequently resulted in the unpredicted extinction of additional gene(s) beside targeted ones. This can be ascribed to uncontrolled genetic material insertions in the genome of the host cell. This approach thus appeared inappropriate to study unknown functions of a gene. Next, we found it possible to specifically extinct a CI subunit gene by direct insertion of a miR targeting CI subunits in a Flp site (HEK293 Flp-In cells). By using this strategy we unambiguously demonstrated that the NDUFB6 subunit is required for complex I activity, and defined conditions suitable to undertake a systematic and stable extinction of the different supernumerary subunits in human cells.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

Detection of Sleeping Beauty transposition in the genome of host cells by non-radioactive Southern blot analysis

The Sleeping Beauty transposon (SB-Tn) system is being used widely as a DNA vector for the delivery of therapeutic transgenes, as well as a tool for the insertional mutagenesis in animal models. In order to accurately assess the insertional potential and properties related to the integration of SB it is essential to determine the copy number of SB-Tn in the host genome. Recently developed SB100X transposase has demonstrated an integration rate that was much higher than the original SB10 and that of other versions of hyperactive SB transposases, such as HSB3 or HSB17. In this study, we have constructed a series of SB vectors carrying either a DsRed or a human β-globin transgene that was encompassed by cHS4 insulator elements, and containing the SB100X transposase gene outside the SB-Tn unit within the same vector in cis configuration. These SB-Tn constructs were introduced into the K-562 erythroid cell line, and their presence in the genomes of host cells was analyzed by Southern blot analysis using non-radioactive probes. Many copies of SB-Tn insertions were detected in host cells regardless of transgene sequences or the presence of cHS4 insulator elements. Interestingly, the size difference of 2.4 kb between insulated SB and non-insulated controls did not reflect the proportional difference in copy numbers of inserted SB-Tns. We then attempted methylation-sensitive Southern blots to assess the potential influence of cHS4 insulator elements on the epigenetic modification of SB-Tn. Our results indicated that SB100X was able to integrate at multiple sites with the number of SB-Tn copies larger than 6 kb in size. In addition, the non-radioactive Southern blot protocols developed here will be useful to detect integrated SB-Tn copies in any mammalian cell type.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2019

Sigma bond activation of deuterium mediated by atomic cerium cations: Experiment and theory

Reaction of ground-state Ce + (5d 2 4f 1 ) with deuterium in a reaction cell at a pressure of 1.5–4.0 Torr and temperatures ranging from approximately 265–515 K is studied. Rate constants for formation of CeD 2 + are acquired and vary from approximately 2.8 × 10 -14 to 2.1 ×10 -13 cm 3 /s. A negative temperature dependence is observed for the measured rate constants, indicating the reaction becomes less efficient as the temperature increases, consistent with an exothermic reaction. Electronic structure calculations were performed using density functional theory (DFT) at the PBE0 level to characterize all reactant and product species as well as to generate potential energy surfaces (PESs) for the insertion reaction. This combination of experimental and theoretical results suggest that Ce + inserts into the deuterium sigma bond in an overall exothermic and barrierless process.

74 ATOMIC AND MOLECULAR PHYSICS↗

DOE OSTI2016

Vaginal Dose Is Associated With Toxicity in Image Guided Tandem Ring or Ovoid-Based Brachytherapy

Purpose: To calculate vaginal doses during image guided brachytherapy with volume-based metrics and correlate with long-term vaginal toxicity. Methods and Materials: In this institutional review board–approved study, institutional databases were searched to identify women undergoing computed tomography and/or magnetic resonance–guided brachytherapy at the Duke Cancer Center from 2009 to 2015. All insertions were contoured to include the vagina as a 3-dimensional structure. All contouring was performed on computed tomography or magnetic resonance imaging and used a 0.4-cm fixed brush to outline the applicator and/or packing, expanded to include any grossly visible vagina. The surface of the cervix was specifically excluded from the contour. High-dose-rate (HDR) and low-dose-rate (LDR) doses were converted to the equivalent dose in 2-Gy fractions using an α/β of 3 for late effects. The parameters D0.1cc, D1cc, and D2cc were calculated for all insertions and summed with prior external beam therapy. Late and subacute toxicity to the vagina were determined by the Common Terminology Criteria for Adverse Events version 4.0 and compared by the median and 4th quartile doses, via the log-rank test. Univariate and multivariate hazard ratios were calculated via Cox regression. Results: A total of 258 insertions in 62 women who underwent definitive radiation therapy including brachytherapy for cervical (n=48) and uterine cancer (n=14) were identified. Twenty HDR tandem and ovoid, 32 HDR tandem and ring, and 10 LDR tandem and ovoid insertions were contoured. The median values (interquartile ranges) for vaginal D0.1cc, D1cc, and D2cc were 157.9 (134.4-196.53) Gy, 112.6 (96.7-124.6) Gy, and 100.5 (86.8-108.4) Gy, respectively. At the 4th quartile cutoff of 108 Gy for D2cc, the rate of late grade 1 toxicity at 2 years was 61.2% (95% confidence interval [CI] 43.0%-79.4%) below 108 Gy and 83.9% (63.9%-100%) above (P=.018); grade 2 or greater toxicity was 36.2% (95% CI 15.8%-56.6%) below 108 Gy and 70.7% (95% CI 45.2%-96.2%) above (P=.004); and grade 3 or worse toxicity was 9.9% (95% CI 0.0%-23.6%) below 108 Gy and 30.0% (95% CI 4.7%-55.3%) above (P=.025). This association was maintained on multivariate analysis, independent of covariates such as applicator type, age, and dose rate. Conclusions: Vaginal dose was associated with all grades of vaginal toxicity. Confirmation at other sites using this methodology will be necessary to establish reproducibility; however, the integration of routine calculation of vaginal dose may be warranted.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2011

Effect of transition element doping on crystal structure of rare earth borosilicides REB{sub 44}Si{sub 2}

On a previous study on samples of doped-YB{sub 44}Si{sub 2}, an improvement of thermoelectric properties has been achieved. Regarding the interesting effect of the doping of transition elements on the thermoelectric properties, a single crystal study has been carried out on Zn doped, Rh doped and Ni doped samples to assess how the transition element doping affects the crystal structure. Refinements were carried out based on the structural model solution of YB{sub 44}Si{sub 2} reported in a previous study. Variations in the silicon contents were found in the doped single crystals. Splitting of partially occupied sites has also been detected for some of the doped samples. In this paper we present differences in the partial occupations of boron and silicon sites. Possibility of transition elements insertions based on the differences in crystal structures will be presented. - Graphical Abstract: New transition elements doped YB{sub 44}Si{sub 2} were synthesized and have nominal compositions YB{sub 41.1}Si{sub 1.1}Rh{sub 0.02} and YB{sub 41}Si{sub 1.3}Ni{sub 0.06}. Insertion of transition elements into the crystal structure of YB{sub 44}Si{sub 2} leads to the transformation of B{sub 12} icosahedra into B{sub 11} polyhedrons for a few percent of them. Highlights: > Differences in the partial occupations of boron and silicon sites{yields}Possibility of transition elements insertions. > Mixed occupancy of split positions. > Insertion of transition elements between B{sub 12} icosahedra.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

DOE OSTI2018

Dynamic imaging of metastable reaction pathways in lithiated cobalt oxide electrodes

Understanding how lithium-ion batteries function down to the atomic level during charge and discharge cycling can provide valuable guidance to optimize structure-property relationships and to design and understand new electrode materials. Lithium insertion and reactions with the electrodes during charge and discharge cycling can occur via metastable structures with complex ordering and related non-equilibrium phenomena. Remarkably, these processes remain still poorly understood despite their significance in the operation of lithium battery systems in critical technologies. In this communication, we present the dynamics of lithium insertion into Co3O4 and the evolution of metastable phases as probed by in-situ transmission electron microscopy, in concert with first principles density functional theory calculations. We show that the initial lithium intercalation reaction occurs with the formation of several metastable and intermediate phases, followed by a sequence of conversion reactions that perturb and expand the cubic-close-packed oxygen array, ultimately generating an end-product of finely dispersed cobalt metal clusters within a Li2O matrix. The calculated non-equilibrium lithiation pathways corroborate with the experimental lithiation voltages, and explain the significant hysteresis that occurs during electrochemical cycling. The data provide new insights into the complexity of solid state lithium electrochemistry in metal oxides that are relevant to advancing lithium battery technology.

conversion reaction electrode↗

DOE OSTI2023

Ultrasonic measurement of temperature distributions in extreme environments: Electrical power plants testing in utility-scale steam generators

Thermal heterogeneities within energy conversion and storage, material processing, nuclear processes, aerospace, and military applications are often inaccessible to characterization by insertion sensors. When sensor deployment is possible, conventional pointwise temperature probes quickly degrade when inserted into harsh environments typical of such processes. We developed spatially-resolved ultrasonic thermometry to noninvasively measure the spatial distributions of thermal properties in such applications, even when sizable thermal gradients are present. Our method divides the path of ultrasonic propagation into segments bound by echogenic features, which create echoes in pulse-echo mode, encoding the information about interior temperature distributions. We use the acquired ultrasonic responses to estimate the internal temperature distributions by solving an inverse problem or concatenating segmental estimates. This work describes the implementation and industrial testing of the developed method at a coal-fired electrical power generation plant. We inserted an echogenically segmented Inconel 625 waveguide into the combustion zone of the utility-scale boiler and continuously acquired ultrasonic data while keeping sensitive components away from the damaging combustion environment. The accuracy of the time-dependent temperature distributions reconstructed from the ultrasonic measurements was comparable to that of thermocouples. The resiliency of ultrasonic thermometry to harsh combustion conditions was far superior to conventional insertion sensors. The measurements obtained during plant operation captured daily steam generation cycles in response to changing customer demand and intermittent contributions of renewable power sources to the power grid. These measurements have revealed new insights into the relationship between the dynamic power generation load and the conditions inside the steam generator. As a result, the successful industrial testing of spatially-resolved ultrasonic thermometry in solids indicates that the developed technology has matured to become an attractive alternative to conventional sensing in solving challenging problems of long-term thermal characterizations in extreme environments.

42 ENGINEERING↗

DOE OSTI2012

Essential role of the unordered VP2 n-terminal domain of the parvovirus MVM capsid in nuclear assembly and endosomal enlargement of the virion fivefold channel for cell entry

The unordered N-termini of parvovirus capsid proteins (Nt) are translocated through a channel at the icosahedral five-fold axis to serve for virus traffick. Heterologous peptides were genetically inserted at the Nt of MVM to study their functional tolerance to manipulations. Insertion of a 5T4-single-chain antibody at VP2-Nt (2Nt) yielded chimeric capsid subunits failing to enter the nucleus. The VEGFR2-binding peptide (V1) inserted at both 2Nt and VP1-Nt efficiently assembled in virions, but V1 disrupted VP1 and VP2 entry functions. The VP2 defect correlated with restricted externalization of V1-2Nt out of the coat. The specific infectivity of MVM and wtVP-pseudotyped mosaic MVM-V1 virions, upon heating and/or partial 2Nt cleavage, demonstrated that some 2Nt domains become intracellularly translocated out of the virus shell and cleaved to initiate entry. The V1 insertion defines a VP2-driven endosomal enlargement of the channel as an essential structural rearrangement performed by the MVM virion to infect.

60 APPLIED LIFE SCIENCES↗