Comment on `Experimental and Theoretical Constraints of Bipolaronic Superconductivity in High TcT_{c} Materials: An Impossibility'

We show that objections raised by Chakraverty $et$ $al$ (Phys. Rev. Lett. 81, 433 (1998)) to the bipolaron model of superconducting cuprates are the result of an incorrect approximation for the bipolaron energy spectrum and misuse of the bipolaron theory. The consideration, which takes into account the multiband energy structure of bipolarons and the unscreened electron-phonon interaction clearly indicates that cuprates are in the Bose-Einstein condensation regime with mobile charged bosons.Comment: 1 page, no figure

Post-mining neutralization of acidic surface mine lakes

Twenty core samples and 54 surface sediment samples were taken from surface mine lakes in Missouri, Illinois, and Indiana to determine the rates of neutralization of acid mine lakes. Sediment samples were analyzed for diatom microfossils, selected chemical elements, and the radionuclide, lead-210. The surface samples showed that there were strong differences in diatom microfossils between acidic and neutral lakes but there was no strong difference in sediment chemical composition between acidic and neutral lakes. Of 20 lakes from which cores were examined, 9 showed diatom evidence of neutralization and one of acidification over time. Cores from 5 of these were dated using lead-210 analysis. Diatom microfossils showed that neutralization took from less than 3 years to 30 years to occur. Comparisons between lake sediment and water column chemistry indicated that neither sulfide deposition nor H2S outgasing is likely to play a major role in the neutralization process. Chemical analyses of lake sediment showed that the sediment is a sink for heavy metals. These metals are held as sulfides. There is also a considerable fraction of metal ions strongly bound to clays. This research demonstrates that acid lake neutralization is common, that it occurs over moderate time spans and that the rate is controlled by rates of acid supply from the watershed.U.S. Department of the InteriorU.S. Geological SurveyOpe

Disorder Effects in the Bipolaron System Ti4_{4}O7_{7} Studied by Photoemission Spectroscopy

We have performed a photoemission study of Ti$_{4}$O$_{7}$ around its two transition temperatures so as to cover the metallic, high-temperature insulating (bipolaron-liquid), and low-temperature insulating (bipolaron-crystal) phases. While the spectra of the low-temperature insulating phase show a finite gap at the Fermi level, the spectra of the high-temperature insulating phase are gapless, which is interpreted as a soft Coulomb gap due to dynamical disorder. We suggest that the spectra of the high-temperature disordered phase of Fe$_{3}$O$_{4}$, which exhibits a charge order-disorder transition (Verwey transition), can be interpreted in terms of a Coulomb gap.Comment: 4 pages, 3 epsf figures embedde

Memory in a magnetic nanoparticle system: polydispersity and interaction effects

We report here a theory of relaxation of single domain magnetic nanoparticles, appropriate for analyzing measurements of Mossbauer spectra, magnetization response, and hysteretic coercivity. Our special focus of attention in the theoretical formulation is the presence of dipolar interaction between the magnetic particles. We discuss in detail the effect of interaction as well as particle size distribution on the measured relaxation spectra and irreversible, nonequilibrium magnetization response in field-cooled and zero-field-cooled situations. Some of the memory effects, similar to those seen in spin glass systems, may be put to important device applications by tuning the interaction and the particle size

Dendritic Cells Cross-Present Immunogenic Lentivector-Encoded Antigen from Transduced Cells to Prime Functional T Cell Immunity

Recombinant lentiviral vectors (LVs) are highly effective vaccination vehicles that elicit protective T cell immunity in disease models. Dendritic cells (DCs) acquire antigen at sites of vaccination and migrate to draining lymph nodes, where they prime vaccine-specific T cells. The potency with which LVs activate CD8+ T cell immunity has been attributed to the transduction of DCs at the immunization site and durable presentation of LV-encoded antigens. However, it is not known how LV-encoded antigens continue to be presented to T cells once directly transduced DCs have turned over. Here, we report that LV-encoded antigen is efficiently cross-presented by DCs in vitro. We have further exploited the temporal depletion of DCs in the murine CD11c.DTR (diphtheria toxin receptor) model to demonstrate that repopulating DCs that were absent at the time of immunization cross-present LV-encoded antigen to T cells in vivo. Indirect presentation of antigen from transduced cells by DCs is sufficient to prime functional effector T cells that control tumor growth. These data suggest that DCs cross-present immunogenic antigen from LV-transduced cells, thereby facilitating prolonged activation of T cells in the absence of circulating LV particles. These are findings that may impact on the future design of LV vaccination strategies

Expression of a dominant T-cell receptor can reduce toxicity and enhance tumor protection of allogeneic T-cell therapy

Due to the lack of specificity for tumor antigens, allogeneic T-cell therapy is associated with graft-versus-host disease. Enhancing the anti-tumor specificity while reducing the graft-versus-host disease risk of allogeneic T cells has remained a research focus. In this study, we demonstrate that the introduction of ‘dominant’ T-cell receptors into primary murine T cells can suppress the expression of endogenous T-cell receptors in a large proportion of the gene-modified T cells. Adoptive transfer of allogeneic T cells expressing a ‘dominant’ T-cell receptor significantly reduced the graft-versus-host toxicity in recipient mice. Using two bone marrow transplant models, enhanced anti-tumor activity was observed in the presence of reduced graft-versus-host disease. However, although transfer of T-cell receptor gene-modified allogeneic T cells resulted in the elimination of antigen-positive tumor cells and improved the survival of treated mice, it was associated with accumulation of T cells expressing endogenous T-cell receptors and the development of delayed graft-versus-host disease. The in vivo deletion of the engineered T cells, mediated by endogenous mouse mammary tumor virus MTV8 and MTV9, abolished graft-versus-host disease while retaining significant anti-tumor activity of adoptively transferred T cells. Together, this study shows that the in vitro selection of allogeneic T cells expressing high levels of a ‘dominant’ T-cell receptor can lower acute graft-versus-host disease and enhance anti-tumor activity of adoptive cell therapy, while the in vivo outgrowth of T cells expressing endogenous T-cell receptors remains a risk factor for the delayed onset of graft-versus-host disease

Adoptive transfer of cytomegalovirus-specific CTL to stem cell transplant patients after selection by HLA–peptide tetramers

Stem cell transplantation is used widely in the management of a range of diseases of the hemopoietic system. Patients are immunosuppressed profoundly in the early posttransplant period, and reactivation of cytomegalovirus (CMV) remains a significant cause of morbidity and mortality. Adoptive transfer of donor-derived CMV-specific CD8(+) T cell clones has been shown to reduce the rate of viral reactivation; however, the complexity of this approach severely limits its clinical application. We have purified CMV-specific CD8(+) T cells from the blood of stem cell transplant donors using staining with HLA-peptide tetramers followed by selection with magnetic beads. CMV-specific CD8(+) cells were infused directly into nine patients within 4 h of selection. Median cell dosage was 8.6 x 10(3)/kg with a purity of 98% of all T cells. CMV-specific CD8(+) T cells became detectable in all patients within 10 d of infusion, and TCR clonotype analysis showed persistence of infused cells in two patients studied. CMV viremia was reduced in every case and eight patients cleared the infection, including one patient who had a prolonged history of CMV infection that was refractory to antiviral therapy. This novel approach to adoptive transfer has considerable potential for antigen-specific T cell therapy