Addition of H_2O and O_2 to Acetone and Dimethylsulfoxide Ligated Uranyl(V) Dioxocations

Gas-phase complexes of the formula [UO_2(lig)]^+ (lig = acetone (aco) or dimethylsulfoxide (dmso)) were generated by electrospray ionization (ESI) and studied by tandem ion-trap mass spectrometry to determine the general effect of ligand charge donation on the reactivity of UO_2^+ with respect to water and dioxygen. The original hypothesis that addition of O_2 is enhanced by strong σ-donor ligands bound to UO_2^+ is supported by results from competitive collision-induced dissociation (CID) experiments, which show near exclusive loss of H_2O from [UO_2(dmso)(H_2O)(O_2)]^+, whereas both H_2O and O_2 are eliminated from the corresponding [UO_2(aco)(H_2O)(O_2)]^+ species. Ligand-addition reaction rates were investigated by monitoring precursor and product ion intensities as a function of ion storage time in the ion-trap mass spectrometer: these experiments suggest that the association of dioxygen to the UO_2^+ complex is enhanced when the more basic dmso ligand was coordinated to the metal complex. Conversely, addition of H_2O is favored for the analogous complex ion that contains an aco ligand. Experimental rate measurements are supported by density function theory calculations of relative energies, which show stronger bonds between UO_2^+ and O_2 when dmso is the coordinating ligand, whereas bonds to H_2O are stronger for the aco complex

One naive T cell, multiple fates in CD8+ T cell differentiation

The mechanism by which the immune system produces effector and memory T cells is largely unclear. To allow a large-scale assessment of the development of single naive T cells into different subsets, we have developed a technology that introduces unique genetic tags (barcodes) into naive T cells. By comparing the barcodes present in antigen-specific effector and memory T cell populations in systemic and local infection models, at different anatomical sites, and for TCR–pMHC interactions of different avidities, we demonstrate that under all conditions tested, individual naive T cells yield both effector and memory CD8+ T cell progeny. This indicates that effector and memory fate decisions are not determined by the nature of the priming antigen-presenting cell or the time of T cell priming. Instead, for both low and high avidity T cells, individual naive T cells have multiple fates and can differentiate into effector and memory T cell subsets

Three dimensional multi-pass repair weld simulations

Full 3-dimensional (3-D) simulation of multi-pass weld repairs is now feasible and practical given the development of improved analysis tools and significantly greater computer power. This paper presents residual stress results from 3-D finite element (FE) analyses simulating a long (arc length of 62°) and a short (arc length of 20°) repair to a girth weld in a 19.6 mm thick, 432 mm outer diameter cylindrical test component. Sensitivity studies are used to illustrate the importance of weld bead inter-pass temperature assumptions and to show where model symmetry can be used to reduce the analysis size. The predicted residual stress results are compared with measured axial, hoop and radial through-wall profiles in the heat affected zone of the test component repairs. A good overall agreement is achieved between neutron diffraction and deep hole drilling measurements and the prediction at the mid-length position of the short repair. These results demonstrate that a coarse 3-D FE model, using a ‘block-dumped’ weld bead deposition approach (rather than progressively depositing weld metal), can accurately capture the important components of a short repair weld residual stress field. However, comparisons of measured with predicted residual stress at mid-length and stop-end positions in the long repair are less satisfactory implying some shortcomings in the FE modelling approach that warrant further investigation

Maturation-Dependent Licensing of Naive T Cells for Rapid TNF Production

The peripheral naïve T cell pool is comprised of a heterogeneous population of cells at various stages of development, which is a process that begins in the thymus and is completed after a post-thymic maturation phase in the periphery. One hallmark of naïve T cells in secondary lymphoid organs is their unique ability to produce TNF rapidly after activation and prior to acquiring other effector functions. To determine how maturation influences the licensing of naïve T cells to produce TNF, we compared cytokine profiles of CD4+ and CD8+ single positive (SP) thymocytes, recent thymic emigrants (RTEs) and mature-naïve (MN) T cells during TCR activation. SP thymocytes exhibited a poor ability to produce TNF when compared to splenic T cells despite expressing similar TCR levels and possessing comparable activation kinetics (upregulation of CD25 and CD69). Provision of optimal antigen presenting cells from the spleen did not fully enable SP thymocytes to produce TNF, suggesting an intrinsic defect in their ability to produce TNF efficiently. Using a thymocyte adoptive transfer model, we demonstrate that the ability of T cells to produce TNF increases progressively with time in the periphery as a function of their maturation state. RTEs that were identified in NG-BAC transgenic mice by the expression of GFP showed a significantly enhanced ability to express TNF relative to SP thymocytes but not to the extent of fully MN T cells. Together, these findings suggest that TNF expression by naïve T cells is regulated via a gradual licensing process that requires functional maturation in peripheral lymphoid organs

Prolonged Antigen Presentation Is Required for Optimal CD8+ T Cell Responses against Malaria Liver Stage Parasites

Immunization with irradiated sporozoites is currently the most effective vaccination strategy against liver stages of malaria parasites, yet the mechanisms underpinning the success of this approach are unknown. Here we show that the complete development of protective CD8+ T cell responses requires prolonged antigen presentation. Using TCR transgenic cells specific for the malaria circumsporozoite protein, a leading vaccine candidate, we found that sporozoite antigen persists for over 8 weeks after immunization—a remarkable finding since irradiated sporozoites are incapable of replication and do not differentiate beyond early liver stages. Persisting antigen was detected in lymphoid organs and depends on the presence of CD11c+ cells. Prolonged antigen presentation enhanced the magnitude of the CD8+ T cell response in a number of ways. Firstly, reducing the time primed CD8+ T cells were exposed to antigen in vivo severely reduced the final size of the developing memory population. Secondly, fully developed memory cells expanded in previously immunized mice but not when transferred to naïve animals. Finally, persisting antigen was able to prime naïve cells, including recent thymic emigrants, to become functional effector cells capable of eliminating parasites in the liver. Together these data show that the optimal development of protective CD8+ T cell immunity against malaria liver stages is dependent upon the prolonged presentation of sporozoite-derived antigen

A mixed valence zinc dithiolene system with spectator metal and reactor ligands

Neutral complexes of zinc with N,N′-diisopropylpiperazine-2,3-dithione (iPr2Dt0) and N,N′-dimethylpiperazine-2,3-dithione (Me2Dt0) with chloride or maleonitriledithiolate (mnt2-) as coligands have been synthesized and characterized. The molecular structures of these zinc complexes have been determined using single crystal X-ray diffractometry. Complexes recrystallize in monoclinic P type systems with zinc adopting a distorted tetrahedral geometry. Two zinc complexes with mixed-valence dithiolene ligands exhibit ligand-to-ligand charge transfer bands. Optimized geometries, molecular vibrations and electronic structures of charge-transfer complexes were calculated using density functional theory (B3LYP/6-311G+(d,p) level). Redox orbitals are shown to be almost exclusively ligand in nature, with a HOMO based heavily on the electron-rich maleonitriledithiolate ligand, and a LUMO comprised mostly of the electron-deficient dithione ligand. Charge transfer is thus believed to proceed from dithiolate HOMO to dithione LUMO, showing ligand-to-ligand redox interplay across a d10 metal