The CD154/CD40 Interaction Required for Retrovirus-Induced Murine Immunodeficiency Syndrome Is Not Mediated by Upregulation of the CD80/CD86 Costimulatory Molecules

C57BL/6 (B6) mice infected with LP-BM5 retroviruses develop disease, including an immunodeficiency similar to AIDS. This disease, murine AIDS (MAIDS), is inhibited by in vivo anti-CD154 monoclonal antibody treatment. The similar levels of insusceptibility of CD40−/− and CD154−/− B6 mice indicate that CD154/CD40 molecular interactions are required for MAIDS. CD4+ T and B cells, respectively, provide the CD154 and CD40 expression needed for MAIDS induction. Here, the required CD154/CD40 interaction is shown to be independent of CD80 and CD86 expression: CD80/CD86−/− B6 mice develop MAIDS after LP-BM5 infection

Heterologous prime-boost-boost immunisation of Chinese cynomolgus macaques using DNA and recombinant poxvirus vectors expressing HIV-1 virus-like particles

Background: There is renewed interest in the development of poxvirus vector-based HIV vaccines due to the protective effect observed with repeated recombinant canarypox priming with gp120 boosting in the recent Thai placebo-controlled trial. This study sought to investigate whether a heterologous prime-boost-boost vaccine regimen in Chinese cynomolgus macaques with a DNA vaccine and recombinant poxviral vectors expressing HIV virus-like particles bearing envelopes derived from the most prevalent clades circulating in sub-Saharan Africa, focused the antibody response to shared neutralising epitopes. Methods: Three Chinese cynomolgus macaques were immunised via intramuscular injections using a regimen composed of a prime with two DNA vaccines expressing clade A Env/clade B Gag followed by boosting with recombinant fowlpox virus expressing HIV-1 clade D Gag, Env and cholera toxin B subunit followed by the final boost with recombinant modified vaccinia virus Ankara expressing HIV-1 clade C Env, Gag and human complement protein C3d. We measured the macaque serum antibody responses by ELISA, enumerated T cell responses by IFN-gamma ELISpot and assessed seroneutralisation of HIV-1 using the TZM-bl beta-galactosidase assay with primary isolates of HIV-1. Results: This study shows that large and complex synthetic DNA sequences can be successfully cloned in a single step into two poxvirus vectors: MVA and FPV and the recombinant poxviruses could be grown to high titres. The vaccine candidates showed appropriate expression of recombinant proteins with the formation of authentic HIV virus-like particles seen on transmission electron microscopy. In addition the b12 epitope was shown to be held in common by the vaccine candidates using confocal immunofluorescent microscopy. The vaccine candidates were safely administered to Chinese cynomolgus macaques which elicited modest T cell responses at the end of the study but only one out of the three macaques elicited an HIV-specific antibody response. However, the antibodies did not neutralise primary isolates of HIV-1 or the V3-sensitive isolate SF162 using the TZM-bl b-galactosidase assay. Conclusions: MVA and FP9 are ideal replication-deficient viral vectors for HIV-1 vaccines due to their excellent safety profile for use in humans. This study shows this novel prime-boost-boost regimen was poorly immunogenic in Chinese cynomolgus macaques

The Relationship Between Diet, Activity, and Other Factors, and Postpartum Weight Change by Race

Objective: To identify the impact of dietary intake and activity level on postpartum weight change. Methods: White (n = 121) and black (n = 224) women, 7-12 months postpartum, participating in the Special Supplemental Feeding Program for Women, Infants, and Children were assessed for dietary intake, activity level, body weight, and other maternal characteristics. Results: For both black and white women, the most important variables in predicting postpartum weight loss were pre-pregnancy weight, gestational weight gain, parity, and prenatal exercise. After these factors were controlled, race predicted that black women retained 6.4 lb more than white women. These results may be due to the finding that black women reported significantly higher mean energy intake (2039 versus 1552 kcal, P \u3c .001), higher percent fat in diet (41 versus 38%, P \u3c .001), and significantly lower amounts of prenatal and postpartum activity. Conclusion: Higher energy intake and lower activity levels in black postpartum mothers compared with white mothers may contribute to the significantly higher rates of obesity found in black mothers. This study suggests the need for intervention strategies in the prenatal and postpartum periods to help those at risk of retaining weight gained during pregnancy

Physiological Basis of the Radioisotope Renogram

A model elucidating the relationships between blood radioactivity, the renogram curve, and urine radioactivity, as a function of time, is derived. Estimation procedures have been devised which use the data from three curves at once to estimate parameters common to the three curves, and which also estimate parameters unique to the individual curves. A program has been written for the RPC 4000 computer to perform the estimation. It was found that some model in which six different exponential parameters could be justified instead of the two proposed by the model could provide a significantly better fit of the data (P \u3c .001), but that the fit under the hypothesis was still quite good

Backflashes from fast-gated avalanche photodiodes in quantum key distribution

InGaAs single-photon avalanche photodiodes (APDs) are key enablers for high-bit rate quantum key distribution. However, the deviation of such detectors from ideal models can open side-channels for an eavesdropper, Eve, to exploit. The phenomenon of backflashes, whereby APDs reemit photons after detecting a photon, gives Eve the opportunity to passively learn the information carried by the detected photon without the need to actively interact with the legitimate receiver, Bob. While this has been observed in slow-gated detectors, it has not been investigated in fast-gated APDs where it has been posited that this effect would be lessened. Here, we perform the first experiment to characterize the security threat that backflashes provide in a GHz-gated self-differencing APD using the metric of information leakage. We find that, indeed, the information leakage is lower than that reported for slower-gated detectors, and we show that its effect on the secure key rate is negligible. We also relate the rate of backflash events to the APD dark current, thereby suggesting that their origin is the InP multiplication region in the APD

Place matters: but does local leadership?

The arrival of New Labour into Government witnessed the prominent re-emergence of place onto the policy agenda. This heralded a range of area-based-initiatives designed to both tackle neighbourhood forms of deprivation and to re-establish a sense of identity and connection between individuals and their local community. In terms of place-making, effective and inclusive participation, representation and leadership were all identified as prerequisites for the creation of sustainable communities . But how important is local leadership and strategic vision within local public service organisations in achieving the desired place-making outcomes? This paper examines the extent to which local leadership and strategic vision represents a significant factor in promoting higher levels of satisfaction, belonging, cohesion and participation across single tier councils in England. The ensuing empirical evidence raises significant questions not only about the importance of local leadership in place-making, but also the environmental and organizational factors that shape local places

Features of successful academic hospitalist programs: Insights from the SCHOLAR (SuCcessful HOspitaLists in academics and research) project

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134172/1/jhm2603.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134172/2/jhm2603-sup-0004-suppinfo4.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134172/3/jhm2603-sup-0001-suppinfo1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134172/4/jhm2603-sup-0010-suppinfo10.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134172/5/jhm2603-sup-0006-suppinfo6.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134172/6/jhm2603-sup-0005-suppinfo5.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134172/7/jhm2603-sup-0009-suppinfo9.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134172/8/jhm2603-sup-0012-suppinfo12.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134172/9/jhm2603-sup-0003-suppinfo3.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134172/10/jhm2603-sup-0002-suppinfo2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134172/11/jhm2603_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134172/12/jhm2603-sup-0008-suppinfo8.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134172/13/jhm2603-sup-0011-suppinfo11.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134172/14/jhm2603-sup-0007-suppinfo7.pd

Party control, party competition and public service performance

publication-status: Acceptedtypes: ArticleThis article assesses party effects on the performance of public services. A policy-seeking model, hypothesizing that left and right party control affects performance, and an instrumental model, where all parties strive to raise performance, are presented. The framework also suggests a mixed model in which party effects are contingent on party competition, with parties raising performance as increasing party competition places their control of government at increasing risk. These models are tested against panel data on English local governments’ party control and public service performance. The results question the traditional account of left and right parties, showing a positive relationship between rightwing party control and performance that is contingent on a sufficiently high level of party competition. The findings suggest left–right models should be reframed for the contemporary context