Improved Pinning Center Morphology in HTS with Order－of－Magnitude Increase in Jc and Bpin Compared to Columnar Pinning

The motivation for continuous columnar pinning centers has been to provide maximum Upin It has been assumed that this provides the best Jc and Bpin. Limitations on Jc and Bpin, observed for columnar pinning have been attributed to degradation of the order parameter and Tc. We examine columnar pinning by ionic damage and cooclude instead that geometrical effects of columnar pinning on percolation path and on the number of pinning centers are the dominant limitations of columnar pinning, leading to a limit of Bpin—4T.Evidence suggests that multiple-in-line-defects (MILD) are far better suited to increase Jc and Bpin,. The morphology of MILD pinning is reviewed. Ion energy loss per unit distance, Se, is found to be most promising in a regime almost diametrically opposite to that sought to maximize Upin. We expect Jc—10^6 A/cm^2 and Bpin＞,40 T from MILD pinning, despite sharply decreased Upin. Experimental confirmation is proposed.     

Demonstration of B-cell maturation in X-linked immunodeficient mice by simultaneous three-colour immunofluorescence

CBA/N mice carrying the X-linked immune deficiency gene (xid) have fewer splenic B cells than normal CBA mice and are unresponsive to a certain class of antigens. Studies of B-cell surface-marker expression and immune responsiveness have led to the commonly accepted idea that the B cells in adult xid mice are immature and resemble the B cells of young (1-3 week old) normal mice. That is, like young animals, xid mice lack cells in the most numerous of three IgM/IgD B-cell subpopulations (designated I in Fig. 1a, b) present in adult spleen. We now report, however, that this picture is an oversimplification and that in fact the B cells in adult xid mice differ from those present in either adult or young normal mice. Using quantitative three-colour fluorescence-activated cell sorter (FACS) analyses, we have compared the correlated expression of IgM, IgD and a newly discovered B-lymphocyte antigen (BLA-1) on splenic B cells in normal and xid mice. We show here (1) that most B cells in adult xid mice (as in normals) are BLA-1- whereas all B cells in young animals are BLA-1+; (2) that the major difference in the IgM/IgD B-cell subpopulations found between xid and normal mice is limited to the BLA-1- cells; and (3) that xid mice have increased numbers of BLA-1+ population III B cells.     

THEMIS observation of a magnetotail current sheet flapping wave

A flapping wave was observed by THEMIS-B （P1） and THEMIS-C （P2） probes on the dawn side of the magnetotail, while the solar wind was generally stable. The magnetic activity was quite weak, suggesting that this flapping wave was generated by an internal instability, which normally occurs during magnetic quiet times. Our analysis shows that the flapping wave was propagating downward with a tail-aligned scale of at least 3.7 RE and did not show much change in shape during its propagation from P1 to P2. Correlation analysis employed to estimate the time lag between the corresponding half waveforms of P1 and P2 shows that the propagating velocities along the current sheet normal directions were close to each other in the beginning, but increased linearly later on. The average wavelength of the flapping wave is approximately 4 RE. Theoretical analysis suggests that the ballooning type wave model may not be the mechanism for the observed flapping wave, but that the magnetic double-gradient instability model is a more plausible candidate.     

Extraintestinal dissemination of Salmonella by CD18-expressing phagocytes.

Specialized epithelia known as M cells overlying the lymphoid follicles of Peyer's patches are important in the mucosal immune system, but also provide a portal of entry for pathogens such as Salmonella typhimurium, Mycobacterium bovis, Shigella flexneri, Yersinia enterocolitica and reoviruses. Penetration of intestinal M cells and epithelial cells by Salmonella typhimurium requires the invasion genes of Salmonella Pathogenicity Island 1 (SPI1). SPI1-deficient S. typhimurium strains gain access to the spleen following oral administration and cause lethal infection in mice without invading M cells or localizing in Peyer's patches, which indicates that Salmonella uses an alternative strategy to disseminate from the gastrointestinal tract. Here we report that Salmonella is transported from the gastrointestinal tract to the bloodstream by CD18-expressing phagocytes, and that CD18-deficient mice are resistant to dissemination of Salmonella to the liver and spleen after oral administration. This CD18-dependent pathway of extraintestinal dissemination may be important for the development of systemic immunity to gastrointestinal pathogens, because oral challenge with SPI1-deficient S. typhimurium elicits a specific systemic IgG humoral immune response, despite an inability to stimulate production of specific mucosal IgA.     

Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine

The acquired immunodeficiency syndrome (AIDS)-causing lentiviruses human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) effectively evade host immunity and, once established, infections with these viruses are only rarely controlled by immunological mechanisms. However, the initial establishment of infection in the first few days after mucosal exposure, before viral dissemination and massive replication, may be more vulnerable to immune control. Here we report that SIV vaccines that include rhesus cytomegalovirus (RhCMV) vectors establish indefinitely persistent, high-frequency, SIV-specific effector memory T-cell (T(EM)) responses at potential sites of SIV replication in rhesus macaques and stringently control highly pathogenic SIV(MAC239) infection early after mucosal challenge. Thirteen of twenty-four rhesus macaques receiving either RhCMV vectors alone or RhCMV vectors followed by adenovirus 5 (Ad5) vectors (versus 0 of 9 DNA/Ad5-vaccinated rhesus macaques) manifested early complete control of SIV (undetectable plasma virus), and in twelve of these thirteen animals we observed long-term (≥1 year) protection. This was characterized by: occasional blips of plasma viraemia that ultimately waned; predominantly undetectable cell-associated viral load in blood and lymph node mononuclear cells; no depletion of effector-site CD4(+) memory T cells; no induction or boosting of SIV Env-specific antibodies; and induction and then loss of T-cell responses to an SIV protein (Vif) not included in the RhCMV vectors. Protection correlated with the magnitude of the peak SIV-specific CD8(+) T-cell responses in the vaccine phase, and occurred without anamnestic T-cell responses. Remarkably, long-term RhCMV vector-associated SIV control was insensitive to either CD8(+) or CD4(+) lymphocyte depletion and, at necropsy, cell-associated SIV was only occasionally measurable at the limit of detection with ultrasensitive assays, observations that indicate the possibility of eventual viral clearance. Thus, persistent vectors such as CMV and their associated T(EM) responses might significantly contribute to an efficacious HIV/AIDS vaccine.     

Discrimination between antibodies to HIV and to related retroviruses using site-directed serology

Human immunodeficiency virus (HIV) strains can be separated into two types: HIV and HIV-related West African viruses. Site-directed serology using synthetic peptides offers possibilities for the determination of type-specific antibodies. A 22-amino-acid peptide with the sequence Ala-Ile-Glu-Lys-Tyr-Leu-Glu-Asp-Gln-Ala-Gln-Leu-Asn-Ala-Trp-Cys-Ala-Phe-Arg-Gln - Val-Cys representing a conserved region of the transmembranous protein of simian T-cell lymphotropic virus-type III (STLV-III; related to West African HIV) was used as antigen in an enzyme-linked immunosorbent assay (ELISA). In parallel, tests were performed with a pair of previously described peptides, including the homologous region of the glycoprotein (gp) 41 of the HIV strain HTLV-IIIB. In tests with three groups of 20 sera it was shown that the different peptide ELISAs allowed a categorical distinction of antibodies to the two types of HIV. Tests using peptide antigens may provide excellent opportunities for large-scale testing for type-specific antibodies against HIV. The tests are simple, sensitive and specific and are readily standardized.