Characterization of aluminum/RP-1 gel propellant properties

Research efforts are being conducted by the NASA Lewis Research Center to formulate and characterize the properties of Al/RP-1 and RP-1 gelled propellants for rocket propulsion systems. Twenty four different compositions of gelled fuels were formulated with 5 and 16 micron, atomized aluminum powder in RP-1. The total solids concentration in the propellant varied from 5 to 60 wt percent. Tests were conducted to evaluate the stability and rheological characteristics of the fuels. Physical separation of the solids occurred in fuels with less than 50 wt percent solids concentration. The rheological characteristics of the Al/RP-1 fuels varied with solids concentration. Both thixotropic and rheopectic gel behavior were observed. The unmetallized RP-1 gels, which were formulated by a different technique than the Al/RP-1 gels, were highly viscoelastic. A history of research efforts which were conducted to formulate and characterize the properties of metallized propellants for various applications is also given

\u3ci\u3eStaphylococcus aureus\u3c/i\u3e Hyaluronidase Is a CodY-Regulated Virulence Factor

Staphylococcus aureus is a Gram-positive pathogen that causes a diverse range of bacterial infections. Invasive S. aureus strains secrete an extensive arsenal of hemolysins, immunomodulators, and exoenzymes to cause disease. Our studies have focused on the secreted enzyme hyaluronidase (HysA), which cleaves the hyaluronic acid polymer at the β-1,4 glycosidic bond. In the study described in this report, we have investigated the regulation and contribution of this enzyme to S. aureus pathogenesis. Using the Nebraska Transposon Mutant Library (NTML), we identified eight insertions that modulate extracellular levels of HysA activity. Insertions in the sigB operon, as well as in genes encoding the global regulators SarA and CodY, significantly increased HysA protein levels and activity. By altering the availability of branched-chain amino acids, we further demonstrated CodY-dependent repression of HysA activity. Additionally, through mutation of the CodY binding box upstream of hysA, the repression of HysA production was lost, suggesting that CodY is a direct repressor of hysA expression. To determine whether HysA is a virulence factor, a ΔhysA mutant of a community-associated methicillin-resistant S. aureus (CA-MRSA) USA300 strain was constructed and found to be attenuated in a neutropenic, murine model of pulmonary infection. Mice infected with this mutant strain exhibited a 4-log-unit reduction in bacterial burden in their lungs, as well as reduced lung pathology and increased levels of pulmonary hyaluronic acid, compared to mice infected with the wild-type, parent strain. Taken together, these results indicate that S. aureus hyaluronidase is a CodY-regulated virulence factor

Prospective surveillance of invasive group a streptococcal disease, Fiji, 2005-2007.

We undertook a prospective active surveillance study of invasive group A streptococcal (GAS) disease in Fiji over a 23-month period, 2005-2007. We identified 64 cases of invasive GAS disease, which represents an average annualized all-ages incidence of 9.9 cases/100,000 population per year (95% confidence interval [CI] 7.6-12.6). Rates were highest in those >65 years of age and in those <5 years, particularly in infants, for whom the incidence was 44.9/100,000 (95% CI 18.1-92.5). The case-fatality rate was 32% and was associated with increasing age and underlying coexisting disease, including diabetes and renal disease. Fifty-five of the GAS isolates underwent emm sequence typing; the types were highly diverse, with 38 different emm subtypes and no particular dominant type. Our data support the view that invasive GAS disease is common in developing countries and deserves increased public health attention

P16-49. Broad types of cytokines secreted by Gag-specific T cells from HIV infected patients on HAART

International audiencen.

Targeting HIV-1 Env gp140 to LOX-1 Elicits Immune Responses in Rhesus Macaques.

Improved antigenicity against HIV-1 envelope (Env) protein is needed to elicit vaccine-induced protective immunity in humans. Here we describe the first tests in non-human primates (NHPs) of Env gp140 protein fused to a humanized anti-LOX-1 recombinant antibody for delivering Env directly to LOX-1-bearing antigen presenting cells, especially dendritic cells (DC). LOX-1, or 1ectin-like oxidized low-density lipoprotein (LDL) receptor-1, is expressed on various antigen presenting cells and endothelial cells, and is involved in promoting humoral immune responses. The anti-LOX-1 Env gp140 fusion protein was tested for priming immune responses and boosting responses in animals primed with replication competent NYVAC-KC Env gp140 vaccinia virus. Anti-LOX-1 Env gp140 vaccination elicited robust cellular and humoral responses when used for either priming or boosting immunity. Co-administration with Poly ICLC, a TLR3 agonist, was superior to GLA, a TLR4 agonist. Both CD4+ and CD8+ Env-specific T cell responses were elicited by anti-LOX-1 Env gp140, but in particular the CD4+ T cells were multifunctional and directed to multiple epitopes. Serum IgG and IgA antibody responses induced by anti-LOX-1 Env gp140 against various gp140 domains were cross-reactive across HIV-1 clades; however, the sera neutralized only HIV-1 bearing sequences most similar to the clade C 96ZM651 Env gp140 carried by the anti-LOX-1 vehicle. These data, as well as the safety of this protein vaccine, justify further exploration of this DC-targeting vaccine approach for protective immunity against HIV-1

IRISS (Increasing Resilience in Surveillance Societies) FP7 European Research Project, Deliverable 4.2: Doing privacy in everyday encounters with surveillance.

The main idea of IRISS WP 4 was to analyse surveillance as an element of everyday life of citizens. The starting point was a broad understanding of surveillance, reaching beyond the narrowly defined and targeted (nonetheless encompassing) surveillance practices of state authorities, justified with the need to combat and prevent crime and terrorism. We were interested in the mundane effects of surveillance practices emerging in the sectors of electronic commerce, telecommunication, social media and other areas. The basic assumption of WP 4 was that being a citizen in modern surveillance societies amounts to being transformed into a techno-social hybrid, i.e. a human being inexorably linked with data producing technologies, becoming a data-leaking container. While this &ldquo;ontological shift&rdquo; is not necessarily reflected in citizens&rsquo; understanding of who they are, it nonetheless affects their daily lives in many different ways. Citizens may entertain ideas of privacy, autonomy and selfhood rooted in pre-electronic times while at the same time acting under a regime of &ldquo;mundane governance&rdquo;. We started to enquire about the use of modern technologies and in the course of the interviews focussed on issues of surveillance in a more explicit manner. Over 200 qualitative interviews were conducted in a way that produced narratives (stories) of individual experiences with different kinds of technologies and/or surveillance practices. These stories then were analysed against the background of theoretical hypotheses of what it means in objective terms to live in a surveillance society. We assume that privacy no longer is the default state of mundane living, but has to be actively created. We captured this with the term privacy labour. Furthermore we construed a number of dilemmas or trade-off situations to guide our analysis. These dilemmas address the issue of privacy as a state or &ldquo;good&rdquo; which is traded in for convenience (in electronic commerce), security (in law enforcement surveillance contexts), sociality (when using social media), mutual trust (in social relations at the workplace as well as in the relationship between citizens and the state), and engagement (in horizontal, neighbourhood watch-type surveillance relations). For each of these dilemmas we identified a number of stories demonstrating how our respondents as &ldquo;heroes&rdquo; in the narrative solved the problems they encountered, strived for the goals they were pursuing or simply handled a dilemmatic situation. This created a comprehensive and multi-dimensional account of the effects of surveillance in everyday life. Each of the main chapters does focus on one of these different dilemmas

Luminescence tuning of MOFs via ligand to metal and metal to metal energy transfer by co-doping of 2∞[Gd2Cl6(bipy)3]*2bipy with europium and terbium

The series of anhydrous lanthanide chlorides LnCl3, Ln=Pr–Tb, and 4,4'-bipyridine (bipy) constitute isotypic MOFs of the formula 2∞[Ln2Cl6(bipy)3]*2bipy. The europium and terbium containing compounds both exhibit luminescence of the referring trivalent lanthanide ions, giving a red luminescence for Eu3+ and a green luminescence for Tb3+ triggered by an efficient antenna effect of the 4,4'-bipyridine linkers. Mixing of different lanthanides in one MOF structure was undertaken to investigate the potential of this MOF system for colour tuning of the luminescence. Based on the gadolinium containing compound, co-doping with different amounts of europium and terbium proves successful and yields solid solutions of the formula 2∞[Gd2-x-yEuxTbyCl6(bipy)3]*2bipy (1–8), 0≤x, y≤0.5. The series of MOFs exhibits the opportunity of tuning the emission colour in-between green and red. Depending on the atomic ratio Gd:Eu:Tb, the yellow region was covered for the first time for an oxygen/carboxylate-free MOF system. In addition to a ligand to metal energy transfer (LMET) from the lowest ligand-centered triplet state of 4,4'-bipyridine, a metal to metal energy transfer (MMET) between 4f-levels from Tb3+ to Eu3+ is as well vital for the emission colour. However, no involvement of Gd3+ in energy transfers is observed rendering it a suitable host lattice ion and connectivity centre for diluting the other two rare earth ions in the solid state. The materials retain their luminescence during activation of the MOFs for microporosity

Signaling via interleukin-4, receptor alpha chain is required for successful vaccination against schistosomiasis in BALB/c mice

Radiation-attenuated (RA) schistosome larvae are potent stimulators of innate immune responses at the skin site of exposure (pinna) that are likely to be important factors in the development of Th1-mediated protective immunity. In addition to causing an influx of neutrophils, macrophages, and dendritic cells (DCs) into the dermis, RA larvae induced a cascade of chemokine and cytokine secretion following in vitro culture of pinna biopsy samples. While macrophage inflammatory protein 1 and interleukin-1 (IL-1) were produced transiently within the first few days, the Th1-promoting cytokines IL-12 and IL-18 were secreted at high levels until at least day 14. Assay of C3H/HeJ mice confirmed that IL-12 secretion was not due to lipopolysaccharide contaminants binding Toll-like receptor 4. Significantly, IL-12 p40 secretion was sustained in pinnae from vaccinated mice but not in those from nonprotected infected mice. In contrast, IL-10 was produced from both vaccinated and infected mice. This cytokine regulates IL-12-associated dermal inflammation, since in vaccinated IL-10/ mice, pinna thickness was greatly increased concurrent with elevated levels of IL-12 p40. A significant number of IL-12 p40 cells were detected as emigrants from in vitro-cultured pinnae, and most were within a population of rare large granular cells that were Ia, consistent with their being antigen-presenting cells. Labeling of IL-12 cells for CD11c, CD205, CD8, CD11b, and F4/80 indicated that the majority were myeloid DCs, although a proportion were CD11c F4/80, suggesting that macrophages were an additional source of IL-12 in the skin

Maintenance therapy of patients with recurrent epithelial ovarian carcinoma with the anti-tumor-associated-mucin-1 antibody gatipotuzumab: results from a double-blind, placebo-controlled, randomized, phase II study

BACKGROUND: Gatipotuzumab is a humanized monoclonal antibody recognizing the carbohydrate-induced epitope of the tumor-associated mucin-1 (TA-MUC1). This study aimed to evaluate the efficacy and safety of switch maintenance therapy with gatipotuzumab in patients with TA-MUC1-positive recurrent ovarian, fallopian tube, or primary high-grade serous peritoneal cancer. PATIENTS AND METHODS: In this double-blind, randomized, placebo-controlled, phase II trial, patients with at least stable disease (SD) following chemotherapy were randomized 2:1 to receive intravenous gatipotuzumab (500 mg followed by 1700 mg 1 week later) or placebo every 3 weeks until tumor progression or unacceptable toxicity occurred. Stratification factors were the number of prior chemotherapy lines (2 versus 3-5), response versus SD after the most recent chemotherapy, and progression-free survival (PFS) <6 versus 6-12 months following the prior therapy. Primary endpoint was PFS according to modified immune-related RECIST 1.1 response criteria. Secondary endpoints were PFS at 6 months, safety, overall response rate, CA-125 progression, overall survival, quality of life, and pharmacokinetics. RESULTS: Overall, 216 patients were randomized to gatipotuzumab (n  =  151) or placebo (n  =  65). Median PFS with gatipotuzumab was 3.5 months as compared with 3.5 months with placebo (hazard ratio 0.96, 95% confidence interval 0.69-1.33, P  =  0.80). No advantage for gatipotuzumab over placebo was seen in the secondary efficacy endpoints or in any stratified subgroups. Gatipotuzumab was well tolerated, with mild to moderate infusion-related reactions being the most common adverse events. CONCLUSIONS: Gatipotuzumab switch maintenance therapy does not improve outcome in TA-MUC1-positive ovarian cancer patients. TRIAL REGISTRATION: ClinicalTrials.govNCT01899599; https://clinicaltrials.gov/ct2/show/NCT01899599