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At least 19 records

HCMV gB shares structural and functional properties with gB proteins from other herpesviruses

Glycoprotein B (gB) facilitates HCMV entry into cells by binding receptors and mediating membrane fusion. The crystal structures of gB ectodomains from HSV-1 and EBV are available, but little is known about the HCMV gB structure. Using multiangle light scattering and electron microscopy, we show here that HCMV gB ectodomain is a trimer with the overall shape similar to HSV-1 and EBV gB ectodomains. HCMV gB ectodomain forms rosettes similar to rosettes formed by EBV gB and the postfusion forms of other viral fusogens. Substitution of several bulky hydrophobic residues within the putative fusion loops with more hydrophilic residues reduced rosette formation and abolished cell fusion. We propose that like gB proteins from HSV-1 and EBV, HCMV gB has two internal hydrophobic fusion loops that likely interact with target membranes. Our work establishes structural and functional similarities between gB proteins from three subfamilies of herpesviruses.

60 APPLIED LIFE SCIENCES↗

Mapping regions of Epstein-Barr virus (EBV) glycoprotein B (gB) important for fusion function with gH/gL

Glycoproteins gB and gH/gL are required for entry of Epstein-Barr virus (EBV) into cells, but the role of each glycoprotein and how they function together to mediate fusion is unclear. Analysis of the functional homology of gB from the closely related primate gammaherpesvirus, rhesus lymphocryptovirus (Rh-LCV), showed that EBV gB could not complement Rh gB due to a species-specific dependence between gB and gL. To map domains of gB required for this interaction, we constructed a panel of EBV/Rh gB chimeric proteins. Analysis showed that insertion of Rh gB from residues 456 to 807 restored fusion function of EBV gB with Rh gH/gL, suggesting this region of gB is important for interaction with gH/gL. Split YFP bimolecular complementation (BiFC) provided evidence of an interaction between EBV gB and gH/gL. Together, our results suggest the importance of a gB-gH/gL interaction in EBV-mediated fusion with B cells requiring the region of EBV gB from 456 to 807.

60 APPLIED LIFE SCIENCES↗

Contribution of N-linked glycans on HSV-2 gB to cell–cell fusion and viral entry

HSV-2 is the major cause of genital herpes and its infection increases the risk of HIV-1 acquisition and transmission. HSV-2 glycoprotein B together with glycoproteins D, H and L are indispensable for viral entry, of which gB, as a class III fusogen, plays an essential role. HSV-2 gB has seven potential N-linked glycosylation (N-CHO) sites, but their significance has yet to be determined. For the first time, we systematically analyzed the contributions of N-linked glycans on gB to cell–cell fusion and viral entry. Our results demonstrated that, of the seven potential N-CHO sites on gB, mutation at N390, N483 or N668 decreased cell–cell fusion and viral entry, while mutation at N133 mainly affected protein expression and the production of infectious virus particles by blocking the transport of gB from the endoplasmic reticulum to Golgi. Our findings highlight the significance of N-linked glycans on HSV-2 gB expression and function. - Highlights: • N-linked glycan at N133 is important for gB intracellular trafficking and maturation. • N-linked glycans at N390, N483 and N668 on gB are necessary for optimal cell–cell fusion. • N-linked glycans at N390, N483 and N668 on gB are necessary for optimal viral entry.

60 APPLIED LIFE SCIENCES↗

Precipitates of Cr at Σ3 <110> {112} GB in α-Fe

Precipitates of Cr at Σ3 <110> {112} GB in α-Fe have been studied using molecular dynamics with a two-band embedded atomic model potential. The accumulation and segregation of Cr atoms and the evolution of the GB depend on local Cr concentration and temperature. At the early stage, with the existence of vacancies, the strong attraction of Cr with the GB core provides a pathway for Cr atoms to quickly accumulate within the GB core. With the increase of Cr concentration, the size of Cr dilute precipitates increases dramatically. And the strong segregation of Cr at the GB is observed, when Cr concentration reach 20%. Also, the size of Cr precipitates increases with increasing the temperatures from 300 K to 1000 K. The accumulation and segregation of Cr atoms at the GB lead to significant deformation of the GB structure and the formation of GB steps, causing the displacement and broadening of the GB.

Grain boundary↗

Ovine Herpesvirus 2 Glycoprotein B Complementation Restores Infectivity to a Bovine Herpesvirus 4 gB-Null Mutant

Ovine herpesvirus 2 (OvHV-2) and bovine herpesvirus 4 (BoHV-4) are gamma herpesviruses that belong to the genera Macavirus and Rhadinovirus, respectively. As with all herpesviruses, both OvHV-2 and BoHV-4 express glycoprotein B (gB), which plays an essential role in the infection of host cells. In that context, it has been demonstrated that a BoHV-4 gB-null mutant is unable to infect host cells. In this study, we used homologous recombination to insert OvHV-2 ORF 8, encoding gB, into the BoHV-4 gB-null mutant genome, creating a chimeric BoHV-4 virus carrying and expressing OvHV-2 gB (BoHV-4∆gB/OvHV-2-gB) that was infectious and able to replicate in vitro. We then evaluated BoHV-4∆gB/OvHV-2-gB as a potential vaccine candidate for sheep-associated malignant catarrhal fever (SA-MCF), a fatal disease of ungulates caused by OvHV-2. Using rabbits as a laboratory model for MCF, we assessed the safety, immunogenicity, and efficacy of BoHV-4∆gB/OvHV-2-gB in an immunization/challenge trial. The results showed that while BoHV-4∆gB/OvHV-2-gB was safe and induced OvHV-2 gB-specific humoral immune responses, immunization conferred only 28.5% protection upon challenge with OvHV-2. Therefore, future studies should focus on alternative strategies to express OvHV-2 proteins to develop an effective vaccine against SA-MCF.

Moré, Daniela D. (ORCID:0000000237606757)↗

Sensitivity of Dislocation-GB interactions to simulation setups in atomistic models

Dislocation-grain boundary (GB) interactions play an integral role in strengthening of crystalline materials, and are dependent on external loading conditions and atomic arrangements at the grain boundary. While molecular dynamics (MD) simulations can provide critical insights into relationships between these parameters and the exact interaction, the outcomes are sensitive to the computational setup. Here, in this work, we explore the effect of computational setup (system size, GB orientation and boundary conditions) on stress-controlled dislocation-grain boundary (DGB) reactions using MD simulations for a well-studied copper symmetric $\langle$1 1 2$\rangle$ tilt boundary. The study demonstrates that the DGB reactions (pinning, absorption, transmission, etc.) are sensitive to the system size and the orientation of the GB to the applied stress. Additionally, the current work shows that there is a critical system size for the dislocation-grain boundary reaction stresses to converge, one which was found to be much larger than the setups in comparable MD studies. This was attributed to the specific stress states and the influence of surfaces, fixed or free, as these computational setups are modified. Finally, a stress-controlled setup with minimal model artifacts is examined, and the effect of coupled Schmid and non-Schmid stress components on the dislocation-GB reactions are discussed.

36 MATERIALS SCIENCE↗

Structural basis for membrane anchoring and fusion regulation of the herpes simplex virus fusogen gB

Viral fusogens merge viral and cell membranes during cell penetration. Their ectodomains drive fusion by undergoing large-scale refolding, but little is known about the functionally important regions located within or near the membrane. Here we report the crystal structure of full-length glycoprotein B (gB), the fusogen from herpes simplex virus, complemented by electron spin resonance measurements. The membrane-proximal (MPR), transmembrane (TMD), and cytoplasmic (CTD) domains form a uniquely folded trimeric pedestal beneath the ectodomain, which balances dynamic flexibility with extensive, stabilizing membrane interactions. The postfusion conformation of the ectodomain suggests that the CTD likewise adopted the postfusion form. However, hyperfusogenic mutations, which destabilize the prefusion state of gB, target key interfaces and structural motifs that reinforce the observed CTD structure. Thus, a similar CTD structure must stabilize gB in its prefusion state. In conclusion, our data suggest a model for how this dynamic, membrane-dependent ‘clamp’ controls the fusogenic refolding of gB.

59 BASIC BIOLOGICAL SCIENCES↗

SU-F-T-461: Dosimetric Evaluation of Indigenous Farmer Type Chamber FAR65- GB for Reference Dosimetry of FFF MV Photon Beam

Purpose: Indigenous Farmer type chamber FAR 65 GB is a reference class 0.6 cc ion chamber. It can be used for dosimetric evaluation of photon and high energy electron beams. We studied dosimetric characteristics of the chamber for 6MV and 10MV Flattening filter free FFF photon beams available on trueBEAM STx Linac. Methods: The study was carried out on trueBEAM STx Linac having 6 and 10 MV FFF photon beam with maximum dose rate 1400 and 2400 MU per min respectively. The dosimetric device to be evaluated is Rosalina Instruments FAR 65-GB Ion Chamber with active volume 0.65 cc, total active length 23.1cm, inner diameter of cylinder 6.2mm, wall thickness 0.4mm, inner electrode diameter 1mm. Inner and outer electrodes are made from Aluminium 2.7 gm per cc and graphite 1.82 gm per cc respectively. The ion chamber was placed along central axis of beam at 10cm depth and irradiated for 10cm × 10cm field size at SAD of 100 cm in plastic phantom. We studied Precision, Dose Linearity, Dose Rate dependence, directional dependence, Recombination effect. Recombination effect was determined using standard two-voltage method. Results: 1. Measurements were reproducible std deviation of 0.0105 and type A uncertainty 0.003265 under same set of reference conditions 2. Chamber exhibit dose linearity over a wider dose range. 3. Chamber shows dose rate independence for all available dose rate range. 4. Response of chamber with the angle of incidence of radiation is constant. 5. Recombination correction factors were 1.01848 and 1.02537 for dose rate 1400 and 2400 MU per min resp. Conclusion: Our study reveals that the chamber is prone to saturation effect at dose rate of 2400 MU per min. FAR 65-GB can be used for reference dosimetry of FFF MV photon beam with proper calculation of recombination effect.

60 APPLIED LIFE SCIENCES↗

Constraints on the Location of the Gamma-ray Emission Region for the Gamma-ray-loud Radio Source GB 1310+487

We employ a single-zone leptonic jet model, with synchrotron, synchrotron self-Compton, and external Compton (EC) processes, to reproduce the quasi-simultaneous multi-wavelength spectral energy distributions in active and quiescent states of the narrow-line gamma-ray-loud radio source GB 1310+487. In the case of the EC process, the external seed photons from both the broad line region (BLR) and the dust torus are considered by assuming that the gamma-ray emission region is located at the outside boundary of the BLR and inside the dust torus. Comparing the energy density of external photon fields U{sub BLR} obtained by model fitting with that constrained from the BLR observations. We find that the location of the gamma-ray-emitting region of GB 1310+487 can be tightly constrained at the outer edge of the BLR (the dissipation distance of the γ-ray emission region from central black hole r{sub diss}∼ a few times of R{sub BLR}). The ratio of magnetic energy and emitting-electron energy in the radiation blob (ϵ{sub B}=L{sub B}/L{sub e}) is gradually increased from Flare 1, to Flare 2, to Post-flare, where the magnetic energy increases and the matter energy decreases. These results suggest that the conversion of the magnetic field and the matter (radiation electrons) energy and the location of the γ-ray emission region (or ambient photon field) may play an important role in different radiation states of GB 1310+487.

79 ASTRONOMY AND ASTROPHYSICS↗

Temporal complementarity of marine renewables with wind and solar generation: Implications for GB system benefits

Wave and tidal energy have the potential to provide benefits to power systems with high proportions of stochastic renewable generation. This is particularly applicable with wind and solar photovoltaics, as the offsetting of these renewable resources results in more reliable renewable generation. This study utilises ten metrics to quantify the temporal complementarity and supply-demand balancing requirements of the energy mix in Great Britain, to investigate the potential magnitude of these system benefits. Wave and tidal generation profiles are created using historical resource data and hydrodynamic models. The results show that the inclusion of wave and tidal generation creates a renewable energy mix which is more available under multiple conditions: throughout a year of operation; at times of peak demand; for multiple consecutive hourly time periods; and at times when wind and solar generation are not available. Three regional case studies also show that the inclusion of marine energy allows for improved regional supply-demand matching, reducing instances of energy shortage and excess and potentially relieving transmission congestion at particularly constrained locations within GB. Finally, the implications of these findings are discussed in terms of GB wholesale market operation, system balancing and system security.

16 TIDAL AND WAVE POWER↗

GB 1508+5714, The First Z Greater than 4 Radio-Selected Quasar In X Rays

We report the detection in X ray of a high redshift (z=4.30) radio-loud quasar, GB 1508+5714, the first radio-selected z greater than 4 quasar seen in X rays. The quasar was observed serendipitously with the Einstein observatory lPC at 0.02 +/- 0.003 counts/s. It is ten times brighter than the other two z greater than 4 X-ray detected quasars. The X-ray source is unusually hard, implying either alpha(sub E) less than 0.2, or N(sub H) greater than 10(exp 22) atoms/sq cm (1(sigma) limits) for a simple power-law plus intrinsic (z=4.3) absorption. Intrinsic absorption would make GB 1508+5714 similar to a large fraction of z approx. 3 radio-loud quasars.

Mathur, Smita↗

Biodistribution of the boron carriers boronophenylalanine (BPA) and/or decahydrodecaborate (GB-10) for Boron Neutron Capture Therapy (BNCT) in an experimental model of lung metastases

BNCT was proposed for the treatment of diffuse, non-resectable tumors in the lung. We performed boron biodistribution studies with 5 administration protocols employing the boron carriers BPA and/or GB-10 in an experimental model of disseminated lung metastases in rats. All 5 protocols were non-toxic and showed preferential tumor boron uptake versus lung. Absolute tumor boron concentration values were therapeutically useful (25–76 ppm) for 3 protocols. Dosimetric calculations indicate that BNCT at RA-3 would be potentially therapeutic without exceeding radiotolerance in the lung.

99 GENERAL AND MISCELLANEOUS↗

25 Gb s{sup −1} data transmission using a bismuth-doped fibre amplifier with a gain peak shifted to 1300 nm

Using a bismuth-doped aluminosilicate fibre laser tunable in the range 1130–1210 nm, we have examined the effect of pump wavelength on the gain spectrum of bismuth-doped phosphosilicate fibres in the range 1220–1400 nm. At a pump wavelength of 1195 nm, we obtained a peak gain wavelength of 1300 nm, which is near the centre of the standard range for O-band transmission (1270–1320 nm) in fibre-optic communication links, in particular between data centres. Using a bismuth-doped phosphosilicate fibre amplifier pumped at 1195 nm, we have demonstrated that the transmission distance for a signal from a semiconductor laser diode directly modulated at 25 Gb s{sup −1} [on – off keying (OOK) modulation] can be increased for G.652 fibre from the standard 10 to 80 km or even more. (letters)

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

DISCOVERY OF A KILOPARSEC-SCALE X-RAY/RADIO JET IN THE z = 4.72 QUASAR GB 1428+4217

We report the discovery of a one-sided 3.''6 (24 kpc, projected) long jet in the high-redshift, z = 4.72, quasar GB 1428+4217 in new Chandra X-ray and Very Large Array (VLA) radio observations. This is the highest redshift kiloparsec-scale X-ray/radio jet known. Analysis of archival very long baseline interferometry 2.3 and 8.6 GHz data reveal a faint one-sided jet extending out to {approx}200 pc and aligned to within {approx}30 Degree-Sign of the Chandra/VLA emission. The 3.''6 distant knot is not detected in an archival Hubble Space Telescope image, and its broadband spectral energy distribution is consistent with an origin from inverse Compton scattering of cosmic microwave background photons for the X-rays. Assuming also equipartition between the radiating particles and magnetic field, the implied jet Lorentz factor is Almost-Equal-To 5. This is similar to the other two known z {approx} 4 kpc scale X-ray jet cases and smaller than typically inferred in lower-redshift cases. Although there are still but a few such very high redshift quasar X-ray jets known, for an inverse Compton origin, the present data suggest that they are less relativistic on large scales than their lower-redshift counterparts.

79 ASTRONOMY AND ASTROPHYSICS↗

OTS 1809+314 and the gamma-ray burst GB 790325b

Deep CCD images of the field containing the recurring Optical Transient Source (OTS) 1809+314 recently discovered on archival plates of the Sonneberg Observatory are presented. At the position of OTS 1809+314 no optical counterpart brighter than V = 24.0-24.5, r(Gunn) = 22.0-22.5, and I = 22.0-22.5 is found. In the zero proper motion limit our observations place severe constraints on possible quiescent counterparts. There is no compelling evidence to suggest an association between the historical optical transient source and the gamma-ray burst GB 790325b located about 5 arcmin to the east of OTS 1809+314.

Hartmann, Dieter↗

Fitting a Model to Floating Gate Prompt Charge Loss Test Data for the Samsung 8 Gb SLC NAND Flash Memory

A recent model provides risk estimates for the deprogramming, of initially programmed floating gates, via prompt charge loss produced by an ionizing radiation environment. The environment can be a mixture of electrons, protons, and heavy ions. The model requires several input parameters. Parameters intended to produce conservative risk estimates for the Samsung 8 Gb SLC NAND flash memory are given, subject to some qualifications.

Edmonds, L. D.↗