Development of CD8 alphabeta CTL epitope-based vaccines requires an effective strategy capable of co-delivering large numbers of CTL epitopes. Here we describe a DNA plasmid encoding a polyepitope or ..."polytope" protein, which contained multiple contiguous minimal murine CTL epitopes. Mice vaccinated with this plasmid made MHC-restricted CTL responses to each of the epitopes, and protective CTL were demonstrated in recombinant vaccinia virus, influenza virus, and tumor challenge models. CTL responses generated by polytope DNA plasmid vaccination lasted for 1 yr, could be enhanced by co-delivering a gene for granulocyte-macrophage CSF, and appeared to be induced in the absence of CD4 T cell-mediated help. The ability to deliver large numbers of CTL epitopes using relatively small polytope constructs and DNA vaccination technology should find application in the design of human epitope-based CTL vaccines, in particular in vaccines against EBV, HIV, and certain cancers.
Two independent ground‐based experiments and two satellite‐borne experiments are used to interpret the changes in plasmaspheric composition at the same point in space during moderate geomagnetic ...activity on 22 January and 14 February 2001. Mass density at L = 2.5 was determined from an array of magnetometers on the Antarctic Peninsula, while the electron number density along the same flux tube was determined from analysis of the group delay of man‐made VLF transmissions from north‐east America. The IMAGE satellite RPI experiment provided in situ measurements of the electron number density in passing the equatorial region of the same field line, while the EUV Imager experiment was able to resolve the He+ abundance by looking back toward the same place a few hours later. On 22 January 2001 all measurements were consistent with a moderately disturbed plasmasphere. On 14 February 2001 there appeared to be a significant response of the plasmasphere to the moderate (Kp = 5) activity levels. Both the electron number density and the mass density determined from the ground‐based experiments were markedly higher than on 22 January 2001. Also, the IMAGE RPI gave a markedly lower electron number density than did the ground‐based data; this is explained by differences in the longitude at which the measurements were made and the presence of localized plasmaspheric structures. At Antarctic Peninsula longitudes a He+ column abundance value of 6 × 1010 cm−2 is found to be equivalent to plasmaspheric electron density levels of 3000 cm−3 at L = 2.5. For these conditions the He+ mass abundance was about 12–16% compared with H+. Both decreases and increases in the He+ column abundance measured by the EUV Imager appear to be linearly correlated to changes in the percentage occurrence of He+ as determined from a combination of ground‐based VLF and ULF observations.
A detailed study of hadronic interactions is presented using data recorded with the highly granular CALICE silicon–tungsten electromagnetic calorimeter. Approximately 350,000 selected π− events at ...energies between 2 and 10GeV have been studied. The predictions of several physics models available within the GEANT4 simulation tool kit are compared to this data. A reasonable overall description of the data is observed; the Monte Carlo predictions are within 20% of the data, and for many observables much closer. The largest quantitative discrepancies are found in the longitudinal and transverse distributions of reconstructed energy.
To determine whether autaptic inhibition plays a functional role in the adult hippocampus, the action potential afterhyperpolarisations
(spike AHPs) of CA1 interneurones were investigated in 25 ...basket, three bistratified and eight axo-axonic cells. The spike
AHPs showed two minima in all regular-spiking (5), burst-firing (3) and in many fast-spiking cells (17:28). The fast component
had a time-to-peak (TTP) of 1.2 ± 0.5 ms, the slower TTP was very variable (range of 3.3â103 ms). The AHP width at half-amplitude
(HW) was 12.5 ± 5.7 ms in fast-spiking, 29.3 ± 18 ms in regular-spiking and 99.7 ± 42 ms in burst-firing cells. Axo-axonic
cells never establish autapses, and the fast-spiking variety showed narrow (HW: 3.9 ± 0.7 ms) spike AHPs with only one AHP
minimum (TTP: 0.9 ± 0.1 ms). When challenged with GABA A receptor modulators, spike AHPs in basket and bistratified cells were enhanced by zolpidem (HW by 18.4 ± 6.2 % in 10:15 cells
tested), diazepam (45.2 ± 0.5 %, 6:7), etomidate (43.9 ± 36 %, 6:8) and pentobarbitone sodium (41 %, 1:1), and were depressed
by bicuculline (-41 ± 5.7 %, 5:8) and picrotoxin (-54 %, 1:1), and the enhancement produced by zolpidem was reduced by flumazenil
(-31 ± 13 %, relative to the AHP HW during exposure to zolpidem, 3:4). Neuronal excitability was modulated in parallel. The
spike AHPs of three axo-axonic cells tested showed no sensitivity to etomidate, pentobarbitone or diazepam. Interneurone-to-interneurone
inhibitory postsynaptic potentials (IPSPs), studied with dual intracellular recordings, had time courses resembling those
of the spike AHPs. The IPSP HW was 13.4 ± 2.8 ms in fast-spiking ( n = 16) and 28.7 ± 5.8 ms in regular-spiking/burst-firing cells ( n = 6), and the benzodiazepine1-selective modulator zolpidem strongly enhanced these IPSPs (45 ± 28 %, n = 5). Interneurones with spike AHPs affected by the GABA A receptor ligands exhibited 3.8 ± 1.9 close autaptic appositions. In three basket cells studied at the ultrastructural level
6 of 6, 1 of 2 and 1 of 2 close appositions were confirmed as autapses. Therefore, in the hippocampus autaptic connections
contribute to spike AHPs in many interneurones. These autapses influence neuronal firing and responses to GABA A receptor ligands.
A search for pair-produced doubly charged Higgs bosons has been performed using data samples corresponding to an integrated luminosity of about 614 pb−1 collected with the OPAL detector at LEP at ...centre-of-mass energies between 189 GeV and 209 GeV. No evidence for a signal has been observed. A mass limit of 98.5 GeV/c2 at the 95% confidence level has been set for the doubly charged Higgs particle in left–right symmetric models. This is the first search for doubly charged Higgs bosons at centre-of-mass energies larger than 91 GeV.
The prevalence of hepatitis C virus (HCV) infection in adult patients with a congenital bleeding disorder (CBD) approaches 95% and is a major cause of morbidity and mortality. Histological ...examination of the liver remains the cornerstone of management decisions in patients without a CBD. The reluctance to perform liver biopsies in patients with a CBD has been a major limitation in the management of these patients. We are currently the only haemophilia centre in Australasia performing liver biopsies in patients with a CBD for the purpose of guiding prognostic and therapeutic decisions. We report here the results of our centre's experience with transjugular liver biopsy (TJLB) in patients with a CBD. An adequate specimen for histological assessment was attained from all of the patients. There were no major complications recorded. Patients were hospitalized for ≤ 48 h for haemostasis prophylaxis. The diagnostic specimen obtained from patients was integral in guiding their future management. We suggest that with a coordinated multidisciplinary approach, TJLB can be performed in patients with a CBD. (Intern Med J 2005; 35: 556–559)
We have measured the time response of the emission spectra of In 0.07 Ga 0.93 N quantum wells with widths of 2, 3, and 4nm in GaN following pulsed optical excitation. We observe a blue shift of the ...emission peak during the excitation and a subsequent red shift as the carriers recombine in the 3- and 4-nm wells, and a negligible shift for the 2-nm well. Using a comprehensive theory we are able to fit both the time evolution of the peak emission energy and the integrated emission intensity. The shift of the emission peak (by about 17 meV) arises from the balancing of the change in screening of the internal piezoelectric field as the carrier density changes and bandgap renormalization. We have projected the calculations to quantify the degree of screening at typical threshold carrier densities. At transparency we estimate carrier densities of 4.3times10 16 m -2 and 4.8times10 16 m -2 for the 4- and 3-nm wells, respectively, which reduce the internal piezoelectric field in the well to 0.97times10 8 (4 nm) and 1.03times10 8 (3 nm) Vmiddotm -1 compared with the unscreened value of about 1.23times10 8 Vmiddotm -1 . Thus, a substantial field remains in these wells under laser conditions. We find that this partially screened field is beneficial in reducing the threshold current compared with that of a square well for modal gains up to about 150 cm - 1
PDF
