Mark Edmundson. Song of Ourselves: Walt Whitman and the Fight for Democracy.

Review of Mark Edmundson. Song of Ourselves: Walt Whitman and the Fight for Democracy

The type of adjuvant in whole inactivated influenza a virus vaccines impacts vaccine-associated enhanced respiratory disease

Influenza A virus (IAV) causes a disease burden in the swine industry in the US and is a challenge to prevent due to substantial genetic and antigenic diversity of IAV that circulate in pig populations. Whole inactivated virus (WIV) vaccines formulated with oil-in-water (OW) adjuvant are commonly used in swine. However, WIV-OW are associated with vaccine-associated enhanced respiratory disease (VAERD) when the hemagglutinin and neuraminidase of the vaccine strain are mismatched with the challenge virus. Here, we assessed if different types of adjuvant in WIV vaccine formulations impacted VAERD outcome. WIV vaccines with a swine δ1-H1N2 were formulated with different commercial adjuvants: OW1, OW2, nano-emulsion squalene-based (NE) and gel polymer (GP). Pigs were vaccinated twice by the intramuscular route, 3 weeks apart, then challenged with an H1N1pdm09 three weeks post-boost and necropsied at 5 days post infection. All WIV vaccines elicited antibodies detected using the hemagglutination inhibition (HI) assay against the homologous vaccine virus, but not against the heterologous challenge virus; in contrast, all vaccinated groups had cross-reactive IgG antibody and IFN-γ responses against H1N1pdm09, with a higher magnitude observed in OW groups. Both OW groups demonstrated robust homologous HI titers and cross-reactivity against heterologous H1 viruses in the same genetic lineage. However, both OW groups had severe immunopathology consistent with VAERD after challenge when compared to NE, GP, and non-vaccinated challenge controls. None of the WIV formulations protected pigs from heterologous virus replication in the lungs or nasal cavity. Thus, although the type of adjuvant in the WIV formulation played a significant role in the magnitude of immune response to homologous and antigenically similar H1, none tested here increased the breadth of protection against the antigenically-distinct challenge virus, and some impacted immunopathology after challenge

RTKN2 induces NF-KappaB dependent resistance to intrinsic apoptosis in HEK cells and REgulates BCL-2 genes in human CD4+ lymphocytes

The gene for Rhotekin 2 (RTKN2) was originally identified in a promyelocytic cell line resistant to oxysterol-induced apoptosis. It is differentially expressed in freshly isolated CD4+ T-cells compared with other hematopoietic cells and is down-regulated following activation of the T-cell receptor. However, very little is known about the function of RTKN2 other than its homology to Rho-GTPase effector, rhotekin, and the possibility that they may have similar roles. Here we show that stable expression of RTKN2 in HEK cells enhanced survival in response to intrinsic apoptotic agents; 25-hydroxy cholesterol and camptothecin, but not the extrinsic agent, TNF&alpha;. Inhibitors of NF-KappaB, but not MAPK, reversed the resistance and mitochondrial pro-apoptotic genes, Bax and Bim, were down regulated. In these cells, there was no evidence of RTKN2 binding to the GTPases, RhoA or Rac2. Consistent with the role of RTKN2 in HEK over-expressing cells, suppression of RTKN2 in primary human CD4+ T-cells reduced viability and increased sensitivity to 25-OHC. The expression of the pro-apoptotic genes, Bax and Bim were increased while BCL-2 was decreased. In both cell models RTKN2 played a role in the process of intrinsic apoptosis and this was dependent on either NF-KappaB signaling or expression of downstream BCL-2 genes. As RTKN2 is a highly expressed in CD4+ T-cells it may play a role as a key signaling switch for regulation of genes involved in T-cell survival.<br /

Temperature controlled motion of an antiferromagnet- ferromagnet interface within a dopant-graded FeRh epilayer

Chemically ordered B2 FeRh exhibits a remarkable antiferromagnetic-ferromagnetic phase transition that is first order. It thus shows phase coexistence, usually by proceeding though nucleation at random defect sites followed by propagation of phase boundary domain walls. The transition occurs at a temperature that can be varied by doping other metals onto the Rh site. We have taken advantage of this to yield control over the transition process by preparing an epilayer with oppositely directed doping gradients of Pd and Ir throughout its height, yielding a gradual transition that occurs between 350 K and 500 K. As the sample is heated, a horizontal antiferromagnetic-ferromagnetic phase boundary domain wall moves gradually up through the layer, its position controlled by the temperature. This mobile magnetic domain wall affects the magnetisation and resistivity of the layer in a way that can be controlled, and hence exploited, for novel device applications

Thermal Converter Devices, Systems and Control Methods

A system is provided for reducing exhaust emissions. The system can comprise a series of chambers, an injector head, and a controller. The controller can maintain desired temperature zones and chemical environments inside the series of chambers, and the chambers and structures inside the system 10 can provide a desired travel path for the air, fuel, and untreated exhaust mixture inside

Pre-conceptual Design Assessment of DEMO Remote Maintenance

EDFA, as part of the Power Plant Physics and Technology programme, has been working on the pre-conceptual design of a Demonstration Power Plant (DEMO). As part of this programme, a review of the remote maintenance strategy considered maintenance solutions compatible with expected environmental conditions, whilst showing potential for meeting the plant availability targets. A key finding was that, for practical purposes, the expected radiation levels prohibit the use of complex remote handling operations to replace the first wall. In 2012/13, these remote maintenance activities were further extended, providing an insight into the requirements, constraints and challenges. In particular, the assessment of blanket and divertor maintenance, in light of the expected radiation conditions and availability, has elaborated the need for a very different approach from that of ITER. This activity has produced some very informative virtual reality simulations of the blanket segments and pipe removal that are exceptionally valuable in communicating the complexity and scale of the required operations. Through these simulations, estimates of the maintenance task durations have been possible demonstrating that a full replacement of the blankets within 6 months could be achieved. The design of the first wall, including the need to use sacrificial limiters must still be investigated. In support of the maintenance operations, a first indication of the requirements of an Active Maintenance Facility (AMF) has been elaborated.Comment: 6 pages, 5 figure

Acute Systemic Inflammatory Response to Lipopolysaccharide Stimulation in Pigs Divergently Selected for Residual Feed Intake

Background: It is unclear whether improving feed efficiency by selection for low residual feed intake (RFI) compromises pigs’ immunocompetence. Here, we aimed at investigating whether pig lines divergently selected for RFI had different inflammatory responses to lipopolysaccharide (LPS) exposure, regarding to clinical presentations and transcriptomic changes in peripheral blood cells. Results: LPS injection induced acute systemic inflammation in both the low-RFI and high-RFI line (n = 8 per line). At 4 h post injection (hpi), the low-RFI line had a significantly lower (p= 0.0075) mean rectal temperature compared to the high-RFI line. However, no significant differences in complete blood count or levels of several plasma cytokines were detected between the two lines. Profiling blood transcriptomes at 0, 2, 6, and 24 hpi by RNA-sequencing revealed that LPS induced dramatic transcriptional changes, with 6296 genes differentially expressed at at least one time point post injection relative to baseline in at least one line (n =4 per line) (|log2(fold change)| ≥ log2(1.2); q \u3c 0.05). Furthermore, applying the same cutoffs, we detected 334 genes differentially expressed between the two lines at at least one time point, including 33 genes differentially expressed between the two lines at baseline. But no significant line-by-time interaction effects were detected. Genes involved in protein translation, defense response, immune response, and signaling were enriched in different co-expression clusters of genes responsive to LPS stimulation. The two lines were largely similar in their peripheral blood transcriptomic responses to LPS stimulation at the pathway level, although the low-RFI line had a slightly lower level of inflammatory response than the high-RFI line from 2 to 6 hpi and a slightly higher level of inflammatory response than the high-RFI line at 24 hpi. Conclusions: The pig lines divergently selected for RFI had a largely similar response to LPS stimulation. However, the low-RFI line had a relatively lower-level, but longer-lasting, inflammatory response compared to the high-RFI line. Our results suggest selection for feed efficient pigs does not significantly compromise a pig’sacute systemic inflammatory response to LPS, although slight differences in intensity and duration may occur