Magnetic field dependence of the proximity-induced triplet superconductivity at ferromagnet/superconductor interfaces

Long-ranged superconductor proximity effects recently found in superconductor-ferromagnetic (S-F) systems are generally attributed to the formation of triplet-pairing correlations due to various forms of magnetic inhomogeneities at the S-F interface. In order to investigate this conjecture within a single F layer coupled to a superconductor, we performed scanning tunneling spectroscopy on bilayers of La2/3Ca1/3MnO3 (LCMO) ferromagnetic thin-films grown on high temperature superconducting films of YBa2Cu3O7- (YBCO) or Pr1.85Ca0.15CuO4 (PCCO) under various magnetic fields. We find a strong correlation between the magnitude of superconductor-related spectral features measured on the LCMO layer and the degree of magnetic inhomogeneity controlled by the external magnetic field. This corroborates theoretical predictions regarding the role played by magnetic inhomogeneities in inducing triplet-pairing at S-F interfaces.This research was supported in parts by the joint German-Israeli DIP Project (G.K. and O.M.), the United States-Israel Binational Science Foundation (O.M.), the Harry de Jur Chair in Applied Science (O.M.), the Karl Stoll Chair in advanced materials at the Technion (G.K.), the Leverhulme Trust through an International Network Grant (J.W.A.R., M.G.B. and O.M.) and the Royal Society (J.W.A.R.).This is the accepted manuscript version. The final published version is available from the publishers at http://journals.aps.org/prb/abstract/10.1103/PhysRevB.89.180506. © 2014 AP

Protective Potential of Antioxidant Enzymes as Vaccines for Schistosomiasis in a Non-Human Primate Model

Schistosomiasis remains a major cause of morbidity in the world. The challenge today is not so much in the clinical management of individual patients, but rather in population-based control of transmission in endemic areas. Recent large-scale efforts aimed at limiting schistosomiasis have produced limited success. There is an urgent need for complementary approaches, such as vaccines. We demonstrated previously that anti-oxidant enzymes such as Cu-Zn superoxide dismutase (SOD) and glutathione S peroxidase (GPX), when administered as DNA-based vaccines induced significant levels of protection in inbred mice, greater than the target 40% reduction in worm burden compared to controls set as a minimum by the WHO. These results led us to investigate if immunization of non-human primates with antioxidants would stimulate an immune response that could confer protection, as a prelude for human trials. Issues of vaccine toxicity and safety that were difficult to address in mice were also investigated. All baboons in the study were examined clinically throughout the study and no adverse reactions occurred to the immunization. When our outbred baboons were vaccinated with two different formulations of SOD (SmCT-SOD and SmEC-SOD) or one of GPX (SmGPX), they showed a reduction in worm number to varying degrees, when compared with the control group. More pronounced, vaccinated animals showed decreased bloody diarrhea, days of diarrhea and egg excretion (transmission), as well as reduction of eggs in the liver tissue and in the large intestine (pathology) compared to controls. Specific IgG antibodies were present in sera after immunizations and 10 weeks after challenge infection compared to controls. PBMC, mesenteric and inguinal node cells from vaccinated animals proliferated and produced high levels of cytokines and chemokines in response to crude and recombinant antigens compared with controls. These data demonstrate the potential of antioxidants as vaccine candidates

A review of system dynamics models applied in transportation

It is 20 years since Abbas and Bell [1994. “System Dynamics Applicability to Transportation Modeling.” Transportation Research Part A 28 (5): 373–390] evaluated the strengths and weaknesses of system dynamics (SD) as an approach for modelling in the transportation area. They listed 12 advantages of the approach and in particular suggested it was well suited to strategic issues and that it could provide a useful tool for supporting policy analysis and decision-making in the transport field. This paper sets out a review of over 50 peer-reviewed journal papers since 1994 categorising them by area of application and providing a summary of particular insights raised. The fields of application include the take-up of alternate fuel vehicles, supply chain management affecting transport, highway maintenance, strategic policy, airport infrastructure and airline business cycles and a set of emerging application areas. The paper concludes with recommendations for future application of the SD approach

Intrinsic paramagnetic meissner effect due to s-wave odd-frequency superconductivity

In 1933, Meissner and Ochsenfeld reported the expulsion of magnetic flux, the diamagnetic Meissner effect, from the interior of superconducting lead. This discovery was crucial in formulating the Bardeen-Cooper-Schrieffer (BCS) theory of superconductivity. In exotic superconducting systems BCS theory does not strictly apply. A classical example is a superconductor-magnet hybrid system where magnetic ordering breaks time-reversal symmetry of the superconducting condensate and results in the stabilisation of an odd-frequency superconducting state. It has been predicted that under appropriate conditions, odd-frequency superconductivity should manifest in the Meissner state as fluctuations in the sign of the magnetic susceptibility meaning that the superconductivity can either repel (diamagnetic) or attract (paramagnetic) external magnetic flux. Here we report local probe measurements of faint magnetic fields in a Au/Ho/Nb trilayer system using low energy muons, where antiferromagnetic Ho (4.5 nm) breaks time-reversal symmetry of the proximity induced pair correlations in Au. From depth-resolved measurements below the superconducting transition of Nb we observe a local enhancement of the magnetic field in Au that exceeds the externally applied field, thus proving the existence of an intrinsic paramagnetic Meissner effect arising from an odd-frequency superconducting state.J.W.A.R. acknowledges financial support from the Royal Society through a University Research Fellowship. J.W.A.R. and A.D.B. acknowledge financial support from the UK EPSRC through NanoDTC EP/G037221/1 and the Leverhulme Trust through an International Network Grant (IN-2013-033). A.D.B. also acknowledges additional financial support from the Schiff Foundation. X.L.W. and J.H.Z. acknowledge support from the MOST of China (2015CB921500). J.L. acknowledges support from the Outstanding Academic Fellows programme at NTNU, the Norwegian Research Council Grant (205591, FRINAT, 216700). J. L., J.W.A.R, and A.D.B. finally acknowledge support from the COST Action MP-1201 'Novel Functionalities through Optimized Confinement of Condensate and Fields.' S.L. and M.G.F. acknowledge the support of the EPSRC through Grant No. EP/J01060X. The muSR measurements were performed at the Swiss Muon Source (SµS), at the Paul Scherrer Institute in Villigen, Switzerland. The project has also received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under the NMI3-II Grant number 283883.This is the final version of the article. It first appeared from APS via http://dx.doi.org/10.1103/PhysRevX.5.04102

Candidate Genes for Expansion and Transformation of Hematopoietic Stem Cells by NUP98-HOX Fusion Genes

BACKGROUND: Hox genes are implicated in hematopoietic stem cell (HSC) regulation as well as in leukemia development through translocation with the nucleoporin gene NUP98. Interestingly, an engineered NUP98-HOXA10 (NA10) fusion can induce a several hundred-fold expansion of HSCs in vitro and NA10 and the AML-associated fusion gene NUP98-HOXD13 (ND13) have a virtually indistinguishable ability to transform myeloid progenitor cells in vitro and to induce leukemia in collaboration with MEIS1 in vivo. METHODOLOGY/PRINCIPAL FINDINGS: These findings provided a potentially powerful approach to identify key pathways mediating Hox-induced expansion and transformation of HSCs by identifying gene expression changes commonly induced by ND13 and NA10 but not by a NUP98-Hox fusion with a non-DNA binding homedomain mutation (N51S). The gene expression repertoire of purified murine bone marrow Sca-1+Lin- cells transduced with retroviral vectors encoding for these genes was established using the Affymetrix GeneChip MOE430A. Approximately seventy genes were differentially expressed in ND13 and NA10 cells that were significantly changed by both compared to the ND13(N51S) mutant. Intriguingly, several of these potential Hox target genes have been implicated in HSC expansion and self-renewal, including the tyrosine kinase receptor Flt3, the prion protein, Prnp, hepatic leukemia factor, Hlf and Jagged-2, Jag2. Consistent with these results, FLT3, HLF and JAG2 expression correlated with HOX A cluster gene expression in human leukemia samples. CONCLUSIONS: In conclusion this study has identified several novel Hox downstream target genes and provides important new leads to key regulators of the expansion and transformation of hematopoietic stem cells by Hox

Nanopillar spin filter tunnel junctions with manganite barriers.

The potential of a manganite ferromagnetic insulator in the field of spin-filtering has been demonstrated. For this, an ultrathin film of Sm0.75Sr0.25MnO3 is integrated as a barrier in an epitaxial oxide nanopillar tunnel junction and a high spin polarization of up to 75% at 5 K has been achieved. A large zero-bias anomaly observed in the dynamic conductance at low temperatures is explained in terms of the Kondo scattering model. In addition, a decrease in spin polarization at low bias and hysteretic magneto-resistance at low temperatures are reported. The results open up new possibilities for spin-electronics and suggest exploration of other manganites-based materials for the room temperature spin-filter applications.This work was partially supported by the ERC Advanced Integrators Grant “SUPERSPIN”. B.P. was funded by the Nehru Trust for Cambridge University and St John’s College. The TEM work at Texas A&M was supported by the U.S. National Science Foundation (NSF-DMR 0846504). The authors wish to thank Prof. J. Kumar (IIT Kanpur, India) for help in improving the manuscript.This document is the Accepted Manuscript version of a Published Work that appeared in final form in Nano Letters, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/nl500798

CTLA-4 blockade augments human T lymphocyte-mediated suppression of lung tumor xenografts in SCID mice

Previous studies by others using transplantable murine tumor models have demonstrated that the administration of antibodies that block CTLA-4 interaction with B7 can provoke the elimination of established tumors, and that the tumor suppression is mediated by T-cells and/or cells expressing NK1.1. Studies from our lab have established in a human/severe combined immunodeficient (SCID) mouse chimeric model that autologous peripheral blood leukocytes (PBL) can suppress the growth of tumor xenografts in a PBL dose-dependent fashion, and that this suppression is dependent upon the patient’s T and NK cells. Using this human/mouse chimeric model, we sought to determine whether an antibody blockade of CTLA-4 would enhance the anti-tumor response of a patient’s PBL. It was first important to determine whether the tumor suppression observed in the SCID model was dependent upon CD28/B7 co-stimulation. Blockade of B7 with a human CTLA-4-Ig fusion protein completely abrogated the lymphocyte-mediated tumor suppression, confirming in this model that tumor suppression is dependent upon a CD28/B7 co-stimulation. Using two different CTLA-4 specific monoclonal antibodies, we observed that CTLA-4 blockade significantly enhanced the human lymphocyte-mediated tumor suppression in mice co-engrafted with PBL and tumor cells. This enhancement was observed in both an allogeneic setting (in which the PBL were allogeneic with respect to the tumor) and an autologous setting (in which the PBL and tumor were from the same patient). These results sustain the notion that human anti-tumor immune response can be augmented (in vivo) by blocking the interaction between CTLA-4 and B7.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46864/1/262_2005_Article_668.pd

Bet Hedging in Yeast by Heterogeneous, Age-Correlated Expression of a Stress Protectant

A new experimental approach reveals a bet-hedging strategy in unstressed, clonal yeast cells, whereby they adopt a range of growth states that correlate with expression of a trehalose-synthesis regulator and predict resistance to future stress

Recombinational Landscape and Population Genomics of Caenorhabditis elegans

Recombination rate and linkage disequilibrium, the latter a function of population genomic processes, are the critical parameters for mapping by linkage and association, and their patterns in Caenorhabditis elegans are poorly understood. We performed high-density SNP genotyping on a large panel of recombinant inbred advanced intercross lines (RIAILs) of C. elegans to characterize the landscape of recombination and, on a panel of wild strains, to characterize population genomic patterns. We confirmed that C. elegans autosomes exhibit discrete domains of nearly constant recombination rate, and we show, for the first time, that the pattern holds for the X chromosome as well. The terminal domains of each chromosome, spanning about 7% of the genome, exhibit effectively no recombination. The RIAILs exhibit a 5.3-fold expansion of the genetic map. With median marker spacing of 61 kb, they are a powerful resource for mapping quantitative trait loci in C. elegans. Among 125 wild isolates, we identified only 41 distinct haplotypes. The patterns of genotypic similarity suggest that some presumed wild strains are laboratory contaminants. The Hawaiian strain, CB4856, exhibits genetic isolation from the remainder of the global population, whose members exhibit ample evidence of intercrossing and recombining. The population effective recombination rate, estimated from the pattern of linkage disequilibrium, is correlated with the estimated meiotic recombination rate, but its magnitude implies that the effective rate of outcrossing is extremely low, corroborating reports of selection against recombinant genotypes. Despite the low population, effective recombination rate and extensive linkage disequilibrium among chromosomes, which are techniques that account for background levels of genomic similarity, permit association mapping in wild C. elegans strains