Immunity to MHC class I antigen after direct DNA transfer into skeletal muscle.

Plasmid cDNA encoding the alpha-chain of either membrane-bound (pcRT.45) or secreted (pcRQ.B3) RT1Aa MHC class I Ag were transferred to Lewis (RT1(1)) rat skeletal muscle by direct injection. Rats were challenged 7 days later with an ACI (RT1a) heterotropic heart transplant, and cardiac allograft survival, RT1Aa-specific antibody levels, and frequency of ACI-specific CTL were monitored. Graft rejection was accelerated by > or = 2 days in an Ag-specific and dose-dependent manner in pcRT.45-injected rats. The pcRQ.B3-injected rats also rejected grafts more rapidly; however, graft rejection was accelerated by only 1 day, and graft infiltrates were less pronounced than in pcRT.45-injected rats. Injection of pcRT.45 resulted in an increase in ACI-specific CTL precursor frequency 3 days post-transplant, whereas there was no significant change in rats pretreated with pcRQ.B3 injection. Compared with rats injected with a control plasmid encoding firefly luciferase, transfer of pcRT.45 resulted in an increase in RT1Aa-specific IgG and IgM antibody 3 days after heart transplantation. Transfer of pcRQ.B3 resulted in a similar mean increase in RT1Aa-specific IgG and IgM antibody after transplantation, but the variability from rat to rat was greater, with some animals exhibiting strong priming, and others showing little or no priming by gene injection. Our results suggest that skeletal muscle can express either membrane-bound or secreted MHC class I Ag after gene transfer, but that the membrane-bound form is more immunogenic than the secreted form in the high responder Lewis rat. Direct DNA transfer to skeletal muscle provides a rapid and specific approach to studying immunity to allogeneic MHC Ag

Use of donor serum to prevent passive transfer of hyperacute rejection

Organ transplantation in presensitized recipients continues to be contraindicated for heart and kidney recipients due to the risk of hyperacute rejection, which has no known treatment at this time. We tested whether donor serum, which contains soluble MHC class I antigen, is able to neutralize the effect of anti-donor antibody in the recipient and prevent hyperacute or accelerated rejection. A rat model of passive immunization was used to test the role of anti-donor antibody in hyperacute rejection. Seven of 10 recipients of hyperimmune serum (HyS), derived from Lewis rats (RT1l) following 3 ACI (RT1a) skin grafts, developed hyperacute or accelerated rejection. Intravenous injection of ACI serum prior to the HyS administration prevented hyperacute rejection in all recipients tested. When third-party (Wistar-Furth, RT1u) serum was given to Lewis rats injected with HyS, hyperacute rejection was not abrogated. When examining the mechanism of this effect, a simple antibody blocking phenomenon was found to be unlikely since flow cytometry analysis showed that ACI serum needed to be present at > or = 256-fold excess compared to HyS to block anti-ACI antibody binding to RT1.Aa+cells by 50%. We tested whether the RT1.Aa class I antigen in ACI serum had other biologic properties that resulted in the prolonged graft survival. However, removal of RT1.Aa antigen from ACI serum prior to use in the passive transfer model did not abrogate the graft prolongation observed previously. These data suggest that components of donor serum other than MHC class I antigen may be useful for preventing the antibody-mediated component of hyperacute rejection

Reducing carbon emissions in aquaculture: Using Carbon Disclosures to identify unbalanced mitigation strategies

The production of Scottish Atlantic salmon (Salmo salar) involves a global supply chain with greenhouse gases (GHG) emitted at every step. With the UK government setting a net zero target by 2050, and the Scottish Government having committed to achieving net zero by 2045, the Scottish salmon aquaculture sector now needs to start to develop and implement comprehensive emissions reductions measures. The methods demonstrated here and the identified imbalances in carbon emissions mitigation strategies provide a route to support this process. We use two international aquaculture operators in Scotland, Grieg Seafood and Mowi, as case studies to understand the scale of GHG emissions in the industry, how these compare to mitigation strategies, and where reduction efforts should be focused. Environmental data disclosed to the Carbon Disclosure Project (CDP), which includes in-depth breakdowns of GHG emissions in Scope 1, Scope 2 and Scope 3 categories were used for the first time in this comparison. This was contrasted with interview data from academics, industry experts and NGOs to identify routes to the most effective mitigation and reduction strategy. CDP data successfully identify imbalances between GHG emissions and mitigation strategies, and demonstrate that while Scope 1 emissions in Scottish aquaculture operations are high compared to other countries, Scope 3 emissions represent the majority of emissions. In terms of mitigation, Scope 1 and Scope 2 strategies are adequate, but Scope 3 mitigation strategies do not match the scale of emissions, identifying a potential route for future carbon emission reductions

Quantum delayed-choice experiment with a beam splitter in a quantum superposition

A quantum system can behave as a wave or as a particle, depending on the experimental arrangement. When for example measuring a photon using a Mach-Zehnder interferometer, the photon acts as a wave if the second beam-splitter is inserted, but as a particle if this beam-splitter is omitted. The decision of whether or not to insert this beam-splitter can be made after the photon has entered the interferometer, as in Wheeler's famous delayed-choice thought experiment. In recent quantum versions of this experiment, this decision is controlled by a quantum ancilla, while the beam splitter is itself still a classical object. Here we propose and realize a variant of the quantum delayed-choice experiment. We configure a superconducting quantum circuit as a Ramsey interferometer, where the element that acts as the first beam-splitter can be put in a quantum superposition of its active and inactive states, as verified by the negative values of its Wigner function. We show that this enables the wave and particle aspects of the system to be observed with a single setup, without involving an ancilla that is not itself a part of the interferometer. We also study the transition of this quantum beam-splitter from a quantum to a classical object due to decoherence, as observed by monitoring the interferometer output.Comment: 9 pages, 7 figures, Accepted by Physical Review Letter

“To Plan or ot to Plan:” Serendipitous vs. Organized Travel

The recent invention and popularity of mobile navigation devices have increased the possibility of unplanned, serendipitous travel. To better understand the independent travel market, this study developed a scale for the construct “Style of Independent Travel” (SIT) in order to explore the serendipitous and organized dimensions of travel and their relationship to relevant travel behavior. The scale was included in a survey of visitors to the Rocky Knob area of southwest Virginia. Findings revealed that tourists had a higher preference for travelling spontaneously than following a fixed and organized itinerary and that serendipity and organization in travel was related to travel planning and visitor activities. However, there was no significant relationship between SIT, past visitation, and role of the destination as primary destination or stopover

Structure of the Hemagglutinin Precursor Cleavage Site, a Determinant of Influenza Pathogenicity and the Origin of the Labile Conformation

AbstractThe membrane fusion potential of influenza HA, like many viral membrane-fusion glycoproteins, is generated by proteolytic cleavage of a biosynthetic precursor. The three-dimensional structure of ectodomain of the precursor HA0 has been determined and compared with that of cleaved HA. The cleavage site is a prominent surface loop adjacent to a novel cavity; cleavage results in structural rearrangements in which the nonpolar amino acids near the new amino terminus bury ionizable residues in the cavity that are implicated in the low-pH-induced conformational change. Amino acid insertions at the cleavage site in HAs of virulent avian viruses and those of viruses isolated from the recent severe outbreak of influenza in humans in Hong Kong would extend this surface loop, facilitating intracellular cleavage

“If You Build It, They Will Come”: Relationship between Attraction Features and Intention to Visit

The purpose of this study is to find out what themes and features of a tourist attraction are considered important by tourists, and whether or not these features influence their likelihood of visiting different types of attractions. First, for potential travelers to a rural destination, their likelihood of visiting different types of built tourist attractions was measured. Second, five attraction features (i.e., Experience, Cultural Value, Site Accessibility, Marketing, Leadership) were used to identify potential travelers’ preference. Finally, this study explored whether attraction features influenced potential travelers’ likelihood to visit different types of built attractions. The findings of this study can provide direction for the planning of cultural and heritage tourism

A randomized trial of aspirin on the risk of embolic events in patients with infective endocarditis

AbstractObjectivesThis study examined the effect of aspirin on the risk of embolic events in infective endocarditis (IE).BackgroundEmbolism is a major complication of IE, and studies in animal models have shown that platelet inhibition with aspirin can lead to more rapid vegetation resolution and a lower rate of embolic events.MethodsWe conducted a randomized, double-blinded, placebo-controlled trial of aspirin treatment (325 mg/day) for four weeks in patients with IE to test the hypothesis that the addition of aspirin would reduce the incidence of clinical systemic embolic events. Patients with perivalvular abscess were excluded. Serial cerebral computed tomograms and transesophageal echocardiograms were obtained in a subset of patients.ResultsDuring the four-year study period, 115 patients were enrolled: 60 assigned to aspirin and 55 assigned to placebo. Embolic events occurred in 17 patients (28.3%) on aspirin and 11 patients (20.0%) on placebo, with an odds ratio (OR) of 1.62 (95% confidence interval [CI] 0.68 to 3.86, p = 0.29). There was a trend toward a higher incidence of bleeding in the patients taking aspirin versus placebo (OR 1.92, 95% CI 0.76 to 4.86, p = 0.075). Development of new intracranial lesions was similar in both groups. Aspirin had no effect on vegetation resolution and valvular dysfunction.ConclusionsIn endocarditis patients already receiving antibiotic treatment, the addition of aspirin does not appear to reduce the risk of embolic events and is likely associated with an increased risk of bleeding. Aspirin is not indicated in the early management of patients with IE