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Background. The Shingles Prevention Study (SPS; Department of Veterans Affairs Cooperative Study 403) demonstrated that zoster vaccine was efficacious through 4 years after vaccination. The Short-Term Persistence Substudy (STPS) was initiated after the SPS to further assess the persistence of vaccine efficacy. Methods. The STPS re-enrolled 7320 vaccine and 6950 placebo recipients from the 38 546-subject SPS population. Methods of surveillance, case determination, and follow-up were analogous to those in the SPS. Vaccine efficacy for herpes zoster (HZ) burden of illness, incidence of postherpetic neuralgia (PHN), and incidence of HZ were assessed for the STPS population, for the combined SPS and STPS populations, and for each year through year 7 after vaccination. Results. In the STPS as compared to the SPS, vaccine efficacy for HZ burden of illness decreased from 61.1% to 50.1%, vaccine efficacy for the incidence of PHN decreased from 66.5% to 60.1%, and vaccine efficacy for the incidence of HZ decreased from 51.3% to 39.6%, although the differences were not statistically significant. Analysis of vaccine efficacy in each year after vaccination for all 3 outcomes showed a decrease in vaccine efficacy after year 1, with a further decline thereafter. Vaccine efficacy was statistically significant for the incidence of HZ and the HZ burden of illness through year 5. Conclusions. Vaccine efficacy for each study outcome was lower in the STPS than in the SPS. There is evidence of the persistence of vaccine efficacy through year 5 after vaccination but, vaccine efficacy is uncertain beyond that point.

\"In addition to tracking the evolution of the black Confederate myth, Levin explores the roles that African Americans performed in the army with a particular focus on the relationship between officers and their personal body servants or camp slaves. In contrast to claims that these men served as soldiers in racially integrated regiments, Levin demonstrates that regardless of the dangers faced in camp, on the march and on the battlefield their legal status remained unchanged. Even long after the guns fell silent Confederate veterans and other writers remembered these men as former slaves and not as soldiers. Levin offers an important reminder that how the war is remembered often runs counter to history\"-- Provided by publisher.

The determination of Jupiter’s odd gravitational harmonics by the Juno spacecraft reveals that the observed jet streams extend to about three thousand kilometres below the cloud tops. Probing the depths of Jupiter The Juno mission set out to probe the hidden properties of Jupiter, such as its gravitational field, the depth of its atmospheric jets and its composition beneath the clouds. A collection of papers in this week's issue report some of the mission's key findings. Jupiter's gravitational field varies from pole to pole, but the cause of this asymmetry is unknown. Rotating planets that are squashed at the poles like Jupiter can have a gravity field that is characterized by a solid-body component, plus components that arise from motions in the atmosphere. Luciano Iess and colleagues use Juno's Doppler tracking data to determine Jupiter's gravity harmonics. They find that the north–south asymmetry arises from atmospheric and interior wind flows. To determine the depths of these flows, Yohai Kaspi and colleagues analyse the odd gravitational harmonics and find that the J 3 , J 5 , J 7 and J 9 harmonics are consistent with the jets extending deep into the atmosphere, perhaps as far as 3,000 kilometres. They conclude that the mass of Jupiter's dynamical atmosphere is about one per cent of Jupiter's total mass. The composition of Jupiter beneath its turbulent atmosphere remains a mystery. If different parts of a spinning object rotate at different rates, then the object probably has a fluid composition. Tristan Guillot and colleagues study the even gravitational harmonics and find that, below a depth of about 3,000 kilometres, Jupiter is rotating almost as a solid body. The atmospheric zonal flows extend downwards by more than 2,000 kilometres, but not beyond 3,500 kilometres, as is also the case with the jets. The depth to which Jupiter’s observed east–west jet streams extend has been a long-standing question 1 , 2 . Resolving this puzzle has been a primary goal for the Juno spacecraft 3 , 4 , which has been in orbit around the gas giant since July 2016. Juno’s gravitational measurements have revealed that Jupiter’s gravitational field is north–south asymmetric 5 , which is a signature of the planet’s atmospheric and interior flows 6 . Here we report that the measured odd gravitational harmonics J 3 , J 5 , J 7 and J 9 indicate that the observed jet streams, as they appear at the cloud level, extend down to depths of thousands of kilometres beneath the cloud level, probably to the region of magnetic dissipation at a depth of about 3,000 kilometres 7 , 8 . By inverting the measured gravity values into a wind field 9 , we calculate the most likely vertical profile of the deep atmospheric and interior flow, and the latitudinal dependence of its depth. Furthermore, the even gravity harmonics J 8 and J 10 resulting from this flow profile also match the measurements, when taking into account the contribution of the interior structure 10 . These results indicate that the mass of the dynamical atmosphere is about one per cent of Jupiter’s total mass.

Wnts are lipid-modified morphogens that play critical roles in development principally through engagement of Frizzled receptors. The 3.25 angstrom structure of Xenopus Wnt8 (XWnt8) in complex with mouse Frizzled-8 (Fz8) cysteine-rich domain (CRD) reveals an unusual two-domain Wnt structure, not obviously related to known protein folds, resembling a \"hand\" with \"thumb\" and \"index\" fingers extended to grasp the Fz8-CRD at two distinct binding sites. One site is dominated by a palmitoleic acid lipid group projecting from serine 187 at the tip of Wnt's thumb into a deep groove in the Fz8-CRD. In the second binding site, the conserved tip of Wnt's \"index finger\" forms hydrophobic amino acid contacts with a depression on the opposite side of the Fz8-CRD. The conservation of amino acids in both interfaces appears to facilitate ligand-receptor cross-reactivity, which has important implications for understanding Wnt's functional pleiotropy and for developing Wnt-based drugs for cancer and regenerative medicine.

Although IL-2 has been studied for its immune-stimulating activity against metastatic cancer, its side effects have limited its clinical use; here, an engineered IL-2 ‘superkine’ is shown to have increased activity, particularly in inducing antitumour T cells, but fewer side effects. Engineering an interleukin-2 'superkine' Chris Garcia and colleagues elucidate the molecular mechanism that underlies the sensitization of T cells to the immunostimulatory cytokine interleukin-2 (IL-2). They use this information to engineer a single-chain IL-2 superkine that functions independent of its α-receptor (IL-2Rα or CD25). This new superkine is more efficacious than IL-2 in inducing antitumour T-cell responses and has fewer toxic side effects. The immunostimulatory cytokine interleukin-2 (IL-2) is a growth factor for a wide range of leukocytes, including T cells and natural killer (NK) cells 1 , 2 , 3 . Considerable effort has been invested in using IL-2 as a therapeutic agent for a variety of immune disorders ranging from AIDS to cancer. However, adverse effects have limited its use in the clinic. On activated T cells, IL-2 signals through a quaternary ‘high affinity’ receptor complex consisting of IL-2, IL-2Rα (termed CD25), IL-2Rβ and IL-2Rγ 4 , 5 , 6 , 7 , 8 . Naive T cells express only a low density of IL-2Rβ and IL-2Rγ, and are therefore relatively insensitive to IL-2, but acquire sensitivity after CD25 expression, which captures the cytokine and presents it to IL-2Rβ and IL-2Rγ. Here, using in vitro evolution, we eliminated the functional requirement of IL-2 for CD25 expression by engineering an IL-2 ‘superkine’ (also called super-2) with increased binding affinity for IL-2Rβ. Crystal structures of the IL-2 superkine in free and receptor-bound forms showed that the evolved mutations are principally in the core of the cytokine, and molecular dynamics simulations indicated that the evolved mutations stabilized IL-2, reducing the flexibility of a helix in the IL-2Rβ binding site, into an optimized receptor-binding conformation resembling that when bound to CD25. The evolved mutations in the IL-2 superkine recapitulated the functional role of CD25 by eliciting potent phosphorylation of STAT5 and vigorous proliferation of T cells irrespective of CD25 expression. Compared to IL-2, the IL-2 superkine induced superior expansion of cytotoxic T cells, leading to improved antitumour responses in vivo , and elicited proportionally less expansion of T regulatory cells and reduced pulmonary oedema. Collectively, we show that in vitro evolution has mimicked the functional role of CD25 in enhancing IL-2 potency and regulating target cell specificity, which has implications for immunotherapy.

يتناول كتاب الجديد حول الشرق القديم بدايات الزراعة والرعى-الجديد حول أصل الكتابة-منجزات علم المصرويات السوفييتى-الجديد حول المجتمع البابلى : الألف الأول ق. م-تاريخ حضرموت وحضارتها-الفرضيات القديمة والجديدة عن موطن الأجداد الهندوأوروبى-الدرافيديون : موطن أجدادهم وزمان ومراحل انتشارهم - الإسقوثيون : اكتشافات جديدة-موطن البارثيين-مواد جديدة عن التاريخ القديم والحضارات العريقة فيما وراء القوقاز.