51 research outputs found
Versatile Coordination of Cyclopentadienyl-Arene Ligands and Its Role in Titanium-Catalyzed Ethylene Trimerization
Cationic titanium(IV) complexes with ansa-(η5-cyclopentadienyl,η6-arene) ligands were synthesized and characterized by X-ray crystallography. The strength of the metal-arene interaction in these systems was studied by variable-temperature NMR spectroscopy. Complexes with a C1 bridge between the cyclopentadienyl and arene moieties feature hemilabile coordination behavior of the ligand and consequently are active ethylene trimerization catalysts. Reaction of the titanium(IV) dimethyl cations with CO results in conversion to the analogous cationic titanium(II) dicarbonyl species. Metal-to-ligand backdonation in these formally low-valent complexes gives rise to a strongly bonded, partially reduced arene moiety. In contrast to the η6-arene coordination mode observed for titanium, the more electron-rich vanadium(V) cations [cyclopentadienyl-arene]V(NiPr2)(NC6H4-4-Me)+ feature η1-arene binding, as determined by a crystallographic study. The three different metal-arene coordination modes that we experimentally observed model intermediates in the cycle for titanium-catalyzed ethylene trimerization. The nature of the metal-arene interaction in these systems was studied by DFT calculations.
Plasma Dynamics
Contains research objectives and summary of research on nineteen research projects split into five sections.National Science Foundation (Grant ENG75-06242-A01)U.S. Energy Research and Development Administration (Contract E(11-1)-2766)U.S. Air Force - Office of Scientific Research (Grant AFOSR-77-3143)U.S. Energy Research and Development Administration (Contract EY-76-C2-02-3070.*000
Introducing affinity and selectivity into galectin-targeting nanoparticles with fluorinated glycan ligands
Galectins are potential biomarkers and therapeutic targets. However, galectins display broad affinity towards β-galactosides meaning glycan-based (nano)biosensors lack the required selectivity and affinity. Using a polymer-stabilized nanoparticle biosensing platform, we herein demonstrate that the specificity of immobilised lacto-N-biose towards galectins can be ‘turned on/off’ by using site-specific glycan fluorination and in some cases reversal of specificity can be achieved. The panel of fluoro-glycans were obtained by a chemoenzymatic approach, exploiting BiGalK and BiGalHexNAcP enzymes from Bifidobacterium infantis which are shown to tolerate fluorinated glycans, introducing structural diversity which would be very laborious by chemical methods alone. These results demonstrate that integrating non-natural, fluorinated glycans into nanomaterials can encode unprecedented selectivity with potential applications in biosensing
A bundle Divertor Design for an Advanced Fuel tokamak Reactor
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Expression and Immunogenicity of Sequence-Modified Human Immunodeficiency Virus Type 1 Subtype B pol and gagpol DNA Vaccines
Control of the worldwide AIDS pandemic may require not only preventive but also therapeutic immunization strategies. To meet this challenge, the next generation of human immunodeficiency virus type 1 (HIV-1) vaccines must stimulate broad and durable cellular immune responses to multiple HIV antigens. Results of both natural history studies and virus challenge studies with macaques indicate that responses to both Gag and Pol antigens are important for the control of viremia. Previously, we reported increased Rev-independent expression and improved immunogenicity of DNA vaccines encoding sequence-modified Gag derived from the HIV-1(SF2) strain (J. zur Megede, M. C. Chen, B. Doe, M. Schaefer, C. E. Greer, M. Selby, G. R. Otten, and S. W. Barnett, J. Virol. 74: 2628-2635, 2000). Here we describe results of expression and immunogenicity studies conducted with novel sequence-modified HIV-1(SF2) GagPol and Pol vaccine antigens. These Pol antigens contain deletions in the integrase coding region and were mutated in the reverse transcriptase (RT) coding region to remove potentially deleterious enzymatic activities. The resulting Pol sequences were used alone or in combination with sequence-modified Gag. In the latter, the natural translational frameshift between the Gag and Pol coding sequences was either retained or removed. Smaller, in-frame fusion gene cassettes expressing Gag plus RT or protease plus RT also were evaluated. Expression of Gag and Pol from GagPol fusion gene cassettes appeared to be reduced when the HIV protease was active. Therefore, additional constructs were evaluated in which mutations were introduced to attenuate or inactivate the protease activity. Nevertheless, when these constructs were delivered to mice as DNA vaccines, similar levels of CD8(+) T-cell responses to Gag and Pol epitopes were observed regardless of the level of protease activity. Overall, the cellular immune responses against Gag induced in mice immunized with multigenic gagpol plasmids were similar to those observed in mice immunized with the plasmid encoding Gag alone. Furthermore, all of the sequence-modified pol and gagpol plasmids expressed high levels of Pol-specific antigens in a Rev-independent fashion and were able to induce potent Pol-specific T- and B-cell responses in mice. These results support the inclusion of a gagpol in-frame fusion gene in future HIV vaccine approaches
Enhanced Delivery and Potency of Self-Amplifying mRNA Vaccines by Electroporation in Situ
Nucleic acid-based vaccines such as viral vectors, plasmid DNA (pDNA), and mRNA are being developed as a means to address limitations of both live-attenuated and subunit vaccines. DNA vaccines have been shown to be potent in a wide variety of animal species and several products are now licensed for commercial veterinary but not human use. Electroporation delivery technologies have been shown to improve the generation of T and B cell responses from synthetic DNA vaccines in many animal species and now in humans. However, parallel RNA approaches have lagged due to potential issues of potency and production. Many of the obstacles to mRNA vaccine development have recently been addressed, resulting in a revival in the use of non-amplifying and self-amplifying mRNA for vaccine and gene therapy applications. In this paper, we explore the utility of EP for the in vivo delivery of large, self-amplifying mRNA, as measured by reporter gene expression and immunogenicity of genes encoding HIV envelope protein. These studies demonstrated that EP delivery of self-amplifying mRNA elicited strong and broad immune responses in mice, which were comparable to those induced by EP delivery of pDNA
The influence of strain and activation on the locomotor function of rat ankle extensor muscles
The ankle extensor muscles of the rat have different mechanical and physiological properties, providing a means of studying how changes in locomotor demands influence muscle fascicle behaviour, force and mechanical power output in different populations of muscle fibre types. Muscle fascicle strain, strain rate and activation patterns in the soleus, plantaris and medial gastrocnemius muscles of the rat were quantified from sonomicrometric and myoelectric data, collected during treadmill locomotion under nine velocity/incline conditions. Significant differences in peak-to-peak muscle fascicle strains and strain rates were identified between the three muscles (P0.2 and >1.0 s–1, respectively). The proportion of stride duration that each muscle was active (duty cycle) differed between locomotor conditions as did the timing of the activation and deactivation phases. A simple Hill-based muscle model was used to determine the influence of muscle activation relative to maximum fascicle strain and duty cycle on total force production and mechanical power output, from a slow and a fast muscle fibre, simulated through two peak-to-peak strain cycles (0.1 and 0.3). The predictions of the model did not complement conclusions that may be drawn from the observation of myoelectric timing and fascicle strain trajectories in each of the muscles. The model predicted that changes in mechanical power output were more sensitive to changes in activation parameters than to changes in strain trajectories, with subtle changes in activation phase and duty cycle significantly affecting predicted mechanical power output
Phonetic Distance between Dutch Dialects
Traditional dialectology relies on identifying language features which are common to one dialect area while distinguishing it from others. It has difficulty in dealing with partial matches of features and with nonoverlapping language patterns. This paper applies Levenshtein distance---a measure of string distance---to pronunciations to overcome both of these difficulties. Partial matches may be quantified, and nonoverlapping patterns may be included in weighted averages of phonetic distance. The result accords with traditonal dialectology to a satisfying degree. 1 Introduction This paper applies a string distance measure---Levenshtein distance---to phonetic data in order to obtain a measure of the distance between words in different dialects. The average distance was then interpreted as a measure of the distance between the dialects themselves, which were examined to obtain dialect groups. The transcriptions of one hundred different words as these are pronounced in a sample of twenty ..
Induction of an IFN-Mediated Antiviral Response by a Self-Amplifying RNA Vaccine: Implications for Vaccine Design Response by a Self-Amplifying RNA
RNA-based vaccines have recently emerged as a promising alternative to the use of DNA-based and viral vector vaccines, in part due to the potential to simplify how vaccines are made and facilitate a rapid response to newly emerging infections. SAM vaccines are based on engineered self-amplifying mRNA (SAM) replicons encoding an antigen, formulated with a synthetic delivery system, and induce broad-based immune responses in preclinical animal models.
In our study, in vivo imaging shows that after the immunization SAM antigen expression has an initial gradual increase. Gene expression profiling in injection site tissues from mice immunized with SAM-based vaccine revealed an early and robust induction of type I IFN and IFN-stimulated responses at the site of injection, concurrent with the preliminary reduced SAM antigen expression. This SAM vaccine-induced type I IFN responses has the potential to provide an adjuvant effect on vaccine potency, or, conversely, it might establish a temporary state that limits the initial SAM-encoded antigen expression. To determine the role of the early type I interferon response, SAM vaccines were evaluated in IFN receptor knock-out mice. Our data indicate that minimizing the early type I interferon responses may be a useful strategy to increase primary SAM expression and the resulting vaccine potency. RNA sequence modification, delivery optimization or concurrent use of appropriate compounds might be some of the strategies to finalize this aim
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