Gd Core Research Articles

Fuel performance evaluation of two high burnup PWR core designs during normal operation, control rod withdrawal, and control rod ejection scenarios

There is interest among utilities to extend the current, 18-month operating cycle to 24 months. Economically, this extension would require greater than 5 % enrichment and peak rod average discharge burnup levels above 62 GWd/MTU. A notable challenge of increasing enrichment is the resulting additional excess reactivity encountered during the early stages of fuel life. To accommodate, burnable absorbers beyond soluble boron are introduced into the fuel system. In high burnup fuels, the possibilities of cladding lift-off and fuel melting increase due, in part, to increased rod internal pressures and limited fuel thermal conductivity, respectively. This work collaboratively employs PARCS, RELAP5-3D, and BISON to compare the fuel performance of two high burnup fuel candidates with higher than 5 % enrichment. The fuel performance parameters were compared to current NRC guidance. The results demonstrate an annular fuel design with homogenously blended gadolinium as a burnable absorber operates with greater safety margins during normal operation, allowing for additional operational flexibility. During normal operation, the core design utilizing Integral Fuel Burnable Absorber pins contained fuel pins which reached plenum pressures above 15.5 MPa by the end of the first fuel cycle and fuel pins experienced cladding hoop strains above 1 %. In the Gd core design, only two observed pins experienced plenum pressures above 15.5 MPa and no pins exceeded 1 % cladding hoop strain. During the control rod withdrawal scenario, plenum pressures for pins in both designs marginally exceeded system pressure, however neither experienced excessive hoop strain. The Gd core design experienced a maximum fuel temperature of 2418 K, which is significantly higher than the Integral Fuel Burnable Absorber design at 2157 K, but still within regulatory guidance. We predicted that the fuel in both could return to service after the CRW event. We also predicted that cladding would not fail during the Control Rod Ejection in either core design. Generally, the Integral Fuel Burnable Absorber core design performed with greater safety margin with regards to temperature during normal operation and the transient events. However, the Gd core design performed with greater safety margin regarding plenum pressure and hoop strain limits during normal operation and both transient events.

Gd3+ Complexes for MRI Detection of Zn2+ in the Presence of Human Serum Albumin: Structure-Activity Relationships.

Zn2+-responsive magnetic resonance imaging (MRI) contrast agents are typically composed of a Gd chelate conjugated to a Zn2+-binding moiety via a linker. They allow for Zn2+ detection in the presence of human serum albumin (HSA). In order to decipher the key parameters that drive their Zn2+-dependent MRI response, we designed a pyridine-based ligand, PyAmC2mDPA, and compared the properties of GdPyAmC2mDPA to those of analogue complexes with varying Gd core, Zn-binding moiety, or linker sizes. The stability constants determined by pH potentiometry showed the good selectivity of PyAmC2mDPA for Gd3+ (log KGd = 16.27) versus Zn2+ (log KZn = 13.58), proving that our modified Zn2+-binding DPA moiety prevents the formation of previously observed dimeric species. Paramagnetic relaxation enhancement measurements indicated at least three sites that are available for GdPyAmC2mDPA binding on HSA, as well as a 2-fold affinity increase when Zn2+ is present (KD = 170 μM versus KDZn = 60 μM). Fluorescence competition experiments provided evidence of the higher affinity for site II vs site I, as well as the importance of both the Zn-binding part and the Gd core in generating enhanced HSA affinity in the presence of Zn2+. Finally, an analysis of nuclear magnetic relaxation dispersion (NMRD) data suggested a significantly increased rigidity for the Zn2+-bound system, which is responsible for the Zn2+-dependent relaxivity response.

Receptor Binding-Induced Conformational Changes in Herpes Simplex Virus Glycoprotein D Permit Interaction with the gH/gL Complex to Activate Fusion.

Herpes simplex virus (HSV) requires four essential virion glycoproteins-gD, gH, gL, and gB-for virus entry and cell fusion. To initiate fusion, the receptor binding protein gD interacts with one of two major cell receptors, HVEM or nectin-1. Once gD binds to a receptor, fusion is carried out by the gH/gL heterodimer and gB. A comparison of free and receptor-bound gD crystal structures revealed that receptor binding domains are located within residues in the N-terminus and core of gD. Problematically, the C-terminus lies across and occludes these binding sites. Consequentially, the C-terminus must relocate to allow for both receptor binding and the subsequent gD interaction with the regulatory complex gH/gL. We previously constructed a disulfide bonded (K190C/A277C) protein that locked the C-terminus to the gD core. Importantly, this mutant protein bound receptor but failed to trigger fusion, effectively separating receptor binding and gH/gL interaction. Here, we show that "unlocking" gD by reducing the disulfide bond restored not only gH/gL interaction but fusion activity as well, confirming the importance of C-terminal movement in triggering the fusion cascade. We characterize these changes, showing that the C-terminus region exposed by unlocking is: (1) a gH/gL binding site; (2) contains epitopes for a group (competition community) of monoclonal antibodies (Mabs) that block gH/gL binding to gD and cell-cell fusion. Here, we generated 14 mutations within the gD C-terminus to identify residues important for the interaction with gH/gL and the key conformational changes involved in fusion. As one example, we found that gD L268N was antigenically correct in that it bound most Mabs but was impaired in fusion, exhibited compromised binding of MC14 (a Mab that blocks both gD-gH/gL interaction and fusion), and failed to bind truncated gH/gL, all events that are associated with the inhibition of C-terminus movement. We conclude that, within the C-terminus, residue 268 is essential for gH/gL binding and induction of conformational changes and serves as a flexible inflection point in the critical movement of the gD C-terminus.

Evaluation of the effective temperature change in Gd-based composite wires assessed by static and pulsed-field magnetic measurements

Gd cladded in a seamless 316L austenitic steel tube has been swaged into wires by the powder-in-tube (PIT) technology, resulting in an outer diameter of 1 mm, a wall thickness of approx. 100 µm and a filling factor of around 62 vol%. Such wires provide an advantageous geometry for heat exchangers and have the benefit to protect the Gadolinium, i.e. from corrosion when being in contact with a heat transfer fluid. The magnetocaloric composite has been studied by static and pulsed magnetic-field measurements in order to evaluate the performance of Gd as a core material. By the analysis of magnetization and heat capacity data, the influences of deformation-induced defects on Gadolinium are presented. The subsequent heat treatment at 773 K for 1 h in Ar atmosphere allowed restoring the magnetic properties of the wire after deformation.Data of the pulsed magnetic-field measurements on the Gd-filled PIT-wires and a Gd–core separated from the jacket are presented, with an achievable temperature change of 1.2 K for the wire and 5.2 K for the Gd in 2 T, respectively. A comparison to previously studied La(Fe,Co,Si)13-filled composite wires is included. It indicates that performance losses due to the passive matrix material cannot be overcome only by an increased adiabatic temperature change of the core material, but instead the wire components need to be chosen regarding an optimized heat capacity ratio, as well.

The Conditions of Sedimentation of Gdańsk Bay Sediments (Baltic Sea, Poland) in the Light of Lithological Features and Carbon Content

The research has been carried out for many years, the aim of which is to thoroughly identify sedimentation conditions in the area of the Gulf of Gdańsk. This process is conditioned by many factors, among which the quantity, type and quality of sedimentary material subject to sedimentation, the dynamics of the reservoir, its depth as well as the morphology of the bottom should be mentioned. Research sediments were collected in April 2014, during a research cruise on ORP Heweliusz. Sediment cores with a length of approx. 25 cm were taken in parts of the basin characterized by a different bathymetry, dynamics and a different distance from the main sources of supply of the terrigenous material. The GD core was taken from the Gdańsk Deep, the PB from the Puck Bay and the other two cores within the Gdansk Deep slope: UP near Hel and VR at the level of the Vistula estuary. The sediments from collected cores were subjected to wet sieve analysis and pipette analysis. The obtained results allowed to determine the type of lithological sediment and the calculation of graining indices, on the basis of which the interpretation of the sedimentation conditions was carried out. In the sediments, the carbon content was determined using the Perkin Elmer 2400 CHNS / O elemental analyzer. It was found that clayey silts and silty clays dominated in the PB, UP, GD core throughout the profile. Only in the VR core, there was a clayey sand, which proved that the sedimentation environment is more dynamic, conditioning the deposition and the periodic redeposition of sediments. It is the shallowest located station near the source of supply with terrigenous sediments (estuary of the Vistula). In the surface layer of the cores, the total organic carbon (TOC) content exceeds 4.7% and reaches up to 8.3%. The lowest TOC content, ranging from 0.8 to 2%, was found in the VR core. The total inorganic carbon (TIC) ranged from 0.18% (VR) to 1.77% (UP). In all profiles, both carbon forms decreased with depth. The greatest dynamics of changes in the surface layer of sediments (10 cm) characterized the UP core (4.1–6.6%), while the smallest changes characterized the PB station (4.7–4.9%). The parameter relations indicate a close relationship between the carbon content and the dynamics of the sedimentation environment and the proximity of the power sources.

Boosting Luminance Energy Transfer Efficiency in Upconversion Nanoparticles with an Energy‐Concentrating Zone

AbstractDespite the successful application of upconversion nanoparticles (UCNPs), their low energy transfer efficiency is still a bottleneck to further applications. Here we design UCNPs with a multilayer structure, including an inert NaYF4:Gd core and an energy‐concentrating zone (ECZ), for efficient energy concentration. The ECZ is composed of an emitting layer of NaYF4:Yb,Er and an absorption layer of NaYF4:Nd,Yb with antenna IRDye 800CW to manipulate the energy transfer. The stable and tight packing of 800CW linked originally with a bisphosphonate ligand improves greatly the transfer efficiency. The proximity of the emitting layer to both surface antenna and accepter also decreases energy depletion. Compared to classical UCNPs, the ECZ UCNPs show 3600 times higher luminescence intensity with an energy transfer efficiency near 60 %. In proof‐of‐concept applications, this type of structure was employed for Hg2+ detection and for photodynamic therapy under hypoxic conditions.

Boosting Luminance Energy Transfer Efficiency in Upconversion Nanoparticles with an Energy-Concentrating Zone.

Despite the successful application of upconversion nanoparticles (UCNPs), their low energy transfer efficiency is still a bottleneck to further applications. Here we design UCNPs with a multilayer structure, including an inert NaYF4 :Gd core and an energy-concentrating zone (ECZ), for efficient energy concentration. The ECZ is composed of an emitting layer of NaYF4 :Yb,Er and an absorption layer of NaYF4 :Nd,Yb with antenna IRDye 800CW to manipulate the energy transfer. The stable and tight packing of 800CW linked originally with a bisphosphonate ligand improves greatly the transfer efficiency. The proximity of the emitting layer to both surface antenna and accepter also decreases energy depletion. Compared to classical UCNPs, the ECZ UCNPs show 3600 times higher luminescence intensity with an energy transfer efficiency near 60 %. In proof-of-concept applications, this type of structure was employed for Hg2+ detection and for photodynamic therapy under hypoxic conditions.

Nuclear quantum shape-phase transitions in odd-mass systems

Microscopic signatures of nuclear ground-state shape phase transitions in odd-mass Eu isotopes are explored starting from excitation spectra and collective wave functions obtained by diagonalization of a core-quasiparticle coupling Hamiltonian based on energy density functionals. As functions of the physical control parameter -- the number of nucleons -- theoretical low-energy spectra, two-neutron separation energies, charge isotope shifts, spectroscopic quadrupole moments, and $E2$ reduced transition matrix elements accurately reproduce available data, and exhibit more pronounced discontinuities at neutron number $N=90$, compared to the adjacent even-even Sm and Gd isotopes. The enhancement of the first-order quantum phase transition in odd-mass systems can be attributed to a shape polarization effect of the unpaired proton which, at the critical neutron number, starts predominantly coupling to Gd core nuclei that are characterized by larger quadrupole deformation and weaker proton pairing correlations compared to the corresponding Sm isotopes.

Gadolinium-conjugated star-block copolymer polylysine-modified polyethylenimine as high-performance T 1 MR imaging blood pool contrast agents.

Core–shell copolymers have received widespread attention because of their unique properties, such as suitable for surface modification and increasing the functionality. Thus, they have been increasingly used in many fields including biomedical, pharmaceutical, electronics and optics. Here, a new core–shell copolymer system was developed to synthesize potential blood pool contrast agent (CA) for magnetic resonance imaging (MRI). The novel CA with high T1 relaxivity was synthesized by conjugating gadolinium (Gd) chelators onto star-block copolymer polyethylenimine-grafted poly(l-lysine) (PEI–PLL) nanoparticles (NPs). The T1 relaxivity of PEI–PLL–DTPA–Gd NPs measured on a 7.0 T small animal MRI scanner was 8.289 mM−1 s−1, higher than that of T1 contrast agents widely used in the clinic, such as Gd–DTPA (also known as Magnevist, r1 = 4.273 mM−1 s−1). These results show that PEI–PLL–DTPA–Gd exhibits more efficient T1 MR contrast enhancement compared to Gd–DTPA. More importantly, the PEI–PLL–DTPA–Gd core–shell NPs exhibited extremely low toxicity when measured against the HepG2 cell line over a similar concentration rang of Magnevist. In in vivo experiments, PEI–PLL–DTPA–Gd not only displayed good T1 contrast enhancement for the abdominal aorta, but also showed prolonged blood circulation time compared with Gd–DTPA, which should enable longer acquisition time, for MR and MR angiographic images, with high resolution in clinical practice. PEI–PLL–DTPA–Gd NPs have potential to serve as high T1 relaxivity blood pool MRI CA in the clinic.

Can novel dinuclear Ni–Gd complexes give supplementary information on the Ni–Gd magnetic interaction?

Two new heterodinuclear Ni–Gd complexes with Ni–(O2)–Gd cores, a practically planar one and a highly distorted one, are reported and structurally characterized. DFT calculations allow calculation of the JNiGd interaction parameters, in good agreement with the experimental data. It has been previously shown in such dinuclear complexes with double-phenoxo bridges that the hinge angle, defined as the angle between the O Ni O and O Gd O planes and the Ni–O–Gd angles, involving the bridging oxygen atoms and the metal ions, play a major role in the value of the resulting magnetic interaction. We demonstrate with help of DFT calculations that these parameters are not sufficient to understand the magnetic interaction change observed in the distorted Ni–(O2)–Gd core. This work allows to explain why tripodal ligands yielding face-sharing 3d–Gd complexes with three phenoxo bridges give JNiGd values lower than in planar edge-sharing 3d–Gd complexes. Eventually these geometric changes do not favor the SMM properties of the corresponding Ni–Dy dinuclear complex.

Induction of conformational changes at the N-terminus of herpes simplex virus glycoprotein D upon binding to HVEM and nectin-1

Herpes simplex virus entry is initiated by glycoprotein D (gD) binding to a cellular receptor, such as HVEM or nectin-1. gD is activated by receptor-induced displacement of the C-terminus from the core of the glycoprotein. Binding of HVEM requires the formation of an N-terminal hairpin loop of gD; once formed this loop masks the nectin-1 binding site on the core of gD. We found that HVEM and nectin-1 exhibit non-reciprocal competition for binding to gD. The N-terminus of gD does not spontaneously form a stable hairpin in the absence of receptor and HVEM does not appear to rely on a pre-existing hairpin for binding to gD(3C–38C) mutants. However, HVEM function is affected by mutations that impair optimal hairpin formation. Furthermore, nectin-1 induces a new conformation of the N-terminus of gD. We conclude that the conformation of the N-terminus of gD is actively modified by the direct action of both receptors.

Antibody-Induced Conformational Changes in Herpes Simplex Virus Glycoprotein gD Reveal New Targets for Virus Neutralization

As the receptor-binding protein of herpes simplex virus (HSV), gD plays an essential role in virus entry. In its native state, the last 56 amino acids of the ectodomain C terminus (C-term) occlude binding to its receptors, herpesvirus entry mediator (HVEM) and nectin-1. Although it is clear that movement of the C-term must occur to permit receptor binding, we believe that this conformational change is also a key event for triggering later steps leading to fusion. Specifically, gD mutants containing disulfide bonds that constrain the C-term are deficient in their ability to trigger fusion following receptor binding. In this report, we show that two newly made monoclonal antibodies (MAbs), MC2 and MC5, have virus-neutralizing activity but do not block binding of gD to either receptor. In contrast, all previously characterized neutralizing anti-gD MAbs block binding of gD to a receptor(s). Interestingly, instead of blocking receptor binding, MC2 significantly enhances the affinity of gD for both receptors. Several nonneutralizing MAbs (MC4, MC10, and MC14) also enhanced gD-receptor binding. While MC2 and MC5 recognized different epitopes on the core of gD, these nonneutralizing MAbs recognized the gD C-term. Both the neutralizing capacity and rate of neutralization of virus by MC2 are uniquely enhanced when MC2 is combined with MAb MC4, MC10, or MC14. We suggest that MC2 and MC5 prevent gD from performing a function that triggers later steps leading to fusion and that the epitope for MC2 is normally occluded by the C-term of the gD ectodomain.

Synthesis of Sphere GdN for Magnetic Refrigeration

Spherical GdN material with diameter of 0.85 ∼ 1.0 mm was synthesized by the hot isostatic pressing (HIP) method aiming at the application to the magnetic refrigeration for hydrogen liquefaction. Conditions of the HIP nitridation starting from metallic Gd spheres were investigated to obtain the spherical GdN materials free from unwanted deformation and/or cracks. We found that slower temperature rising rate, 10°C/h, around the melting point of Gd metal, 1300-1600°C, is favorable because it would allow the metallic Gd core to transform into nitride by reacting with nitrogen diffusing from the surface. We have successfully synthesized spherical GdN material of 300 g, which is enough to operate a test device for the magnetic refrigeration. Oxidization degree of this spherical GdN material was investigated by exposing it to air with some controlled humidity. It was found that only 2.5 % of the GdN was degraded after 56 hour exposition to air dried with silica gel.

Mononuclear Cu and dinuclear Cu–Ln complexes of benzimidazole based ligands including N and O donors: Syntheses, characterization, X-ray molecular structures and magnetic properties

The synthesis of two mononuclear precursor copper complexes, [(HL 2) 2Cu], 1, and [(HL 3) 2Cu]·H 2O, 2, and three dinuclear Cu–Ln complexes, [(HL 1) 2Cu(CH 3CN) 2Gd(NO 3) 3], 3, [(HL 3) 2CuGd(NO 3) 3]·2(H 2O), 4, and [(HL 3) 2CuTb(NO 3) 3]·2(H 2O), 5, based on the ligands H 2L 1 (4-bromo-2-[1-(5-bromo-2-hydroxy-3-methoxybenzyl)-1 H-benzimidazol-2-yl]-6-methoxyphenol), H 2L 2 (2-(1 H-benzimidazol-2-yl)-4-bromo-6-methoxyphenol) and H 2L 3 (2-(1 H-benzimidazol-2-yl)-6-methoxyphenol) are described in this contribution. The X-ray crystal structures of H 2L 2, 1, 3, 4, and 5 have been solved. The novel ligand H 2L 2 crystallizes with two independent molecules in the asymmetric unit; several intermolecular hydrogen contacts connect alternate independent H 2L 2 molecules into chains developing along c. In complex 1, two (HL 2) − ligands chelate the copper ion through their imidazolyl nitrogen and phenoxo oxygen atoms, in a relative head to tail arrangement. The molecular structure of 3 is similar to those of the previously reported Cu–Ln complexes of H 2L 1. In the isostructural complexes 4 and 5, two HL 3 ligands sandwich one Cu 2+ ion through their N,O sites and one Ln 3+ ion through their O 2 site, implying a relative head to head arrangement, at variance with the relative head to tail arrangement of HL 2 in the mononuclear copper precursor 1. The magnetic properties of 1, 3, 4, and 5 have been investigated. Extended intermolecular antiferromagnetic interactions operate in complex 1 (( J Chain = −0.8(1) cm −1). Ferromagnetic interactions between Gd ( S = 7/2) and Cu ( S = 1/2) centers operate in complexes 3 and 4, leading to an S = 4 ground state ( J CuGd = 7.2(2) cm −1 for 3 and J CuGd = 6.5(2) cm −1 for 4). Depopulation of the Tb Stark levels, preclude obtaining reliable information on the presence and sign of the Cu–Tb interaction in 5. These new complexes are complementary to those previously reported: the Cu–O 2–Gd core is planar while deformations are borne by the ligands at variance with previous examples where the constraints were located at the Cu–O 2–Gd core. The presence of two independent ligands in the Cu,Gd coordination spheres confers a degree of freedom greater than that allowed by a unique tetradentate ligand. As a result, the strength of the magnetic interaction is not solely related to the dihedral angle between the CuOO and GdOO planes in the central core.

A copper-activated magnetic resonance imaging contrast agent with improved turn-on relaxivity response and anion compatibility

We present the synthesis and characterization of Copper-Gad-7 (CG7), a new copper-activated magnetic resonance imaging (MRI) contrast agent that possesses a Gd(3+)-DO3A scaffold with an appended thioether-rich receptor for copper recognition. Installation of additional carboxylate groups on the periphery of the CG scaffold affords a practical strategy to increase the absolute relaxivity of these types of copper-responsive MRI sensors as well as reduce their sensitivity to biologically abundant anions. Due in large part to restricted access of inner-sphere water molecules to the paramagnetic Gd(3+) core, in the absence of copper ions, CG7 exhibits a relatively low relaxivity value of r(1) = 2.6 mM(-1) s(-1); addition of Cu(+) triggers a 340% enhancement in relaxivity to r(1) = 11.4 mM(-1) s(-1). For comparison, the relaxivity of the analogous CG2 sensor without peripheral carboxylates increases from r(1) = 1.5 to 6.9 mM(-1) s(-1) upon Cu(+) binding. CG7 features high selectivity for Cu(+) over a range of biologically relevant metal ions, including the cellular abundant alkali and alkaline earth cations and d-block ions Zn(2+) and Cu(2+). Moreover, the Cu(+)-response of the CG7 sensor is not significantly affected by bicarbonate, phosphate, citrate, and lactate anions at cellular levels. (17)O NMR dysprosium-induced shift (DIS) and nuclear magnetic relaxation dispersion (NMRD) experiments suggest that the origin of the improved anion compatibility of CG7 is a reduced q modulation compared to previous members of the CG family, and T(1)-weighted phantom images confirm that CG7 can monitor changes in copper levels by MRI at clinically relevant field strengths.

Magnetic Properties of GaGdN Studied by SX-MCD and XAFS

The element-selected magnetic circular dichroism (MCD) between Gd core states is observed in the soft X-ray region (1150-1250 eV). The dichroism intensity for the transition from the 3d to 4f orbital of the Gd atomic state is very strong and reaches up to about 30% at 15 K. The temperature dependence of the MCD intensity shows a ferromagnetic phase around 50-80 K in addition to the room temperature ferromagnetic phase. Its X-ray absorption near edge structure is different from those of other Gd compounds. It seems to be related to the strength of the ferromagnetic behavior.

Copper-Responsive Magnetic Resonance Imaging Contrast Agents

The design, synthesis, and evaluation of the Copper-Gad (CG) family, a new class of copper-activated magnetic resonance imaging (MRI) contrast agents, are presented. These indicators comprise a Gd(3+)-DO3A core coupled to various thioether-rich receptors for copper-induced relaxivity switching. In the absence of copper ions, inner-sphere water binding to the Gd(3+) chelate is restricted, resulting in low longitudinal relaxivity values (r(1) = 1.2-2.2 mM(-1) s(-1) measured at 60 MHz). Addition of Cu(+) to CG2, CG3, CG4, and CG5 and either Cu(+) or Cu(2+) to CG6 triggers marked enhancements in relaxivity (r(1) = 2.3-6.9 mM(-1) s(-1)). CG2 and CG3 exhibit the greatest turn-on responses, going from r(1) = 1.5 mM(-1) s(-1) in the absence of Cu(+) to r(1) = 6.9 mM(-1) s(-1) upon Cu(+) binding (a 360% increase). The CG sensors are highly selective for Cu(+) and/or Cu(2+) over competing metal ions at cellular concentrations, including Zn(2+) at 10-fold higher concentrations. (17)O NMR dysprosium-induced shift and nuclear magnetic relaxation dispersion measurements support a mechanism in which copper-induced changes in the coordination environment of the Gd(3+) core result in increases in q and r(1). T(1)-weighted phantom images establish that the CG sensors are capable of visualizing changes in copper levels by MRI at clinical field strengths.

The multipartite system that mediates entry of herpes simplex virus into the cell

The multipartite entry-fusion system of herpes simplex virus is made of a quartet of glycoproteins-gD, gB, gH.gL-and three alternative gD receptors, herpesvirus entry mediator (HVEM), nectin1 and modified sites on heparan sulphate. This multipartite system recapitulates the basic steps of virus-cell fusion, i.e. receptor recognition, triggering of fusion and fusion execution. Specifically, in addition to serving as the receptor-binding glycoprotein, gD triggers fusion through a specialised domain, named pro-fusion domain (PFD), located C-terminally in the ectodomain. In the unliganded gD the C-terminal region folds around the N-terminal region, such that gD adopts a closed autoinhibited conformation. In HVEM- and nectin1-bound gD the C-terminal region is displaced (opened conformation). gD is the tool for modification of HSV tropism, through insertion of ligands to heterologous tumour-specific receptors. It is discussed whether gD responds to the interaction with the natural and the heterologous receptors by adopting similar conformations, and whether the closed-to-open switch in conformation is a generalised mechanism of activation. A peculiar recombinant highlighted that the central Ig-folded core of gD may not encode executable functions for entry and that the 219-314 aa segment may be sufficient to trigger fusion. With respect to fusion execution, gB appears to be a prospective fusogen based on its coiled-coil trimeric structure, similar to that of another fusion glycoprotein. On the other hand, gH exhibits molecular elements typical of class 1 fusion glycoproteins, in particular heptad repeats and strong tendency to interact with lipids. Whether fusion execution is carried out by gB or gH.gL, or both glycoproteins in complex or sequentially remains to be determined.

Structure and magnetic properties of Gd nanoparticles and carbon coated Gd/GdC2 nanocapsules

Gd nanoparticles and carbon coated Gd/GdC2 nanocapsules have been prepared by means of arc discharge in argon and methane, respectively. In the Gd nanoparticles, gadolinium oxide was detected by x-ray diffraction, while the presence of metallic gadolinium was proved by oxygen analysis and x-ray photoelectron spectra. In the nanocapsules, the existence of GdC2 and Gd was detected by x-ray diffraction. Shell/core structures were observed for either the nanoparticles (with diameters larger than 20 nm) or the nanocapsules. The magnetization data above 25 K, when scaled as a function of μ0H/T, fall on a universal curve while the deviation of the magnetization curves at 4.2 K from the universal curves was ascribed to the superparamagnetism–ferromagnetism transition of small Gd particles. The temperature dependence of magnetization supports the theoretical predictions for very tiny Gd nanoparticles. The presence of metallic Gd in these nanocapsules results in comparatively high magnetization of about 60.5 A m2/kg at 4.2 K, compared with the carbon-coated gadolinium carbide nanocapsules without the metallic Gd core. The possibility of the existence of the spin-glass-like state is discussed for Gd(O) nanoparticles and Gd(C) nanocapsules.

Structure-based mutagenesis of herpes simplex virus glycoprotein D defines three critical regions at the gD-HveA/HVEM binding interface.

Herpes simplex virus (HSV) entry into cells requires the binding of glycoprotein D (gD) to one of several cell surface receptors. The crystal structure of gD bound to one of these receptors, HveA/HVEM, reveals that the core of gD comprises an immunoglobulin fold flanked by a long C-terminal extension and an N-terminal hairpin loop. HveA is a member of the tumor necrosis factor receptor family and contains four cysteine-rich domains (CRDs) characteristic of this family. Fourteen amino acids within the gD N-terminal loop comprise the entire binding site for HveA. To determine the contribution of each gD contact residue to virus entry, we constructed gD molecules mutated in these amino acids. We determined the abilities of the gD mutants to bind receptors, facilitate virus entry, and mediate cell-cell fusion. Seven of the gD mutants exhibited wild-type levels of receptor binding and gD function. Results from the other seven gD mutants revealed three critical regions at the gD-HveA interface. (i) Several gD residues that participate in an intermolecular beta-sheet with HveA were found to be crucial for HveA binding and entry into HveA-expressing cells. (ii) Two gD residues that contact HveA-Y23 contributed to HveA binding but were not required for mediating entry into cells. HveA-Y23 fits into a crevice on the surface of gD and was previously shown to be essential for gD binding. (iii) CRD2 was previously shown to contribute to gD binding, and this study shows that one gD residue that contacts CRD2 contributes to HveA binding. None of the gD mutations prevented interaction with nectin-1, another gD receptor. However, when cotransfected with the other glycoproteins required for fusion, two gD mutants gained the ability to mediate fusion of cells expressing nectin-2, a gD receptor that interacts with several laboratory-derived gD mutants but not with wild-type gD. Thus, results from this panel of gD mutants as well as those of previous studies (A. Carfi, S. H. Willis, J. C. Whitbeck, C. Krummenacher, G. H. Cohen, R. J. Eisenberg, and D. C. Wiley, Mol. Cell 8:169-179, 2001, and S. A. Connolly, D. J. Landsburg, A. Carfi, D. C. Wiley, R. J. Eisenberg, and G. H. Cohen, J. Virol. 76:10894-10904, 2002) provide a detailed picture of the gD-HveA interface and the contacts required for functional interaction. The results demonstrate that of the 35 gD and HveA contact residues that comprise the gD-HveA interface, only a handful are critical for complex formation.