Underexpanded Supersonic Plume Surface Interactions: Applications for Spacecraft Landings on Planetary Bodies

Numerical and experimental investigations of both far-field and near-field supersonic steady jet interactions with a flat surface at various atmospheric pressures are presented in this paper. These studies were done in assessing the landing hazards of both the NASA Mars Science Laboratory and Phoenix Mars spacecrafts. Temporal and spatial ground pressure measurements in conjunction with numerical solutions at altitudes of approx.35 nozzle exit diameters and jet expansion ratios (e) between 0.02 and 100 are used. Data from steady nitrogen jets are compared to both pulsed jets and rocket exhaust plumes at Mach approx.5. Due to engine cycling, overpressures and the plate shock dynamics are different between pulsed and steady supersonic impinging jets. In contrast to highly over-expanded (e 5 (lunar atmospheric regime), the ground pressure is minimal due to the development of a highly expansive shock structure. We show this is dependent on the stability of the plate shock, the length of the supersonic core and plume decay due to shear layer instability which are all a function of the jet expansion ratio. Asymmetry and large gradients in the spatial ground pressure profile and large transient overpressures are predominantly linked to the dynamics of the plate shock. More importantly, this study shows that thruster plumes exhausting into martian environments possess the largest surface pressure loads and can occur at high spacecraft altitudes in contrast to the jet interactions at terrestrial and lunar atmospheres. Theoretical and analytical results also show that subscale supersonic cold gas jets adequately simulate the flow field and loads due to rocket plume impingement provided important scaling parameters are in agreement. These studies indicate the critical importance of testing and modeling plume-surface interactions for descent and ascent of spacecraft and launch vehicles

Quantitative Deep Sequencing Reveals Dynamic HIV-1 Escape and Large Population Shifts during CCR5 Antagonist Therapy In Vivo

High-throughput sequencing platforms provide an approach for detecting rare HIV-1 variants and documenting more fully quasispecies diversity. We applied this technology to the V3 loop-coding region of env in samples collected from 4 chronically HIV-infected subjects in whom CCR5 antagonist (vicriviroc [VVC]) therapy failed. Between 25,000–140,000 amplified sequences were obtained per sample. Profound baseline V3 loop sequence heterogeneity existed; predicted CXCR4-using populations were identified in a largely CCR5-using population. The V3 loop forms associated with subsequent virologic failure, either through CXCR4 use or the emergence of high-level VVC resistance, were present as minor variants at 0.8–2.8% of baseline samples. Extreme, rapid shifts in population frequencies toward these forms occurred, and deep sequencing provided a detailed view of the rapid evolutionary impact of VVC selection. Greater V3 diversity was observed post-selection. This previously unreported degree of V3 loop sequence diversity has implications for viral pathogenesis, vaccine design, and the optimal use of HIV-1 CCR5 antagonists

Influence of Dietary Oil Content and Conjugated Linoleic Acid (CLA) on Lipid Metabolism Enzyme Activities and Gene Expression in Tissues of Atlantic Salmon (Salmo salar L.)

The overall objective is to test the hypothesis that conjugated linoleic acid (CLA) has beneficial effects in Atlantic salmon through affecting lipid and fatty acid metabolism. The specific aims of the present study were to determine the effects of CLA on some key pathways of fatty acid metabolism including fatty acid oxidation and highly unsaturated fatty acid (HUFA) synthesis. Salmon smolts were fed diets containing two levels of fish oil (low, ~18% and high, ~34%) containing three levels of CLA (a 1:1 mixture of 9-cis,trans-11 and trans-10,cis-12 at 0, 1 and 2% of diet) for 3 months. The effects of dietary CLA on HUFA synthesis and β-oxidation were measured and the expression of key genes in the fatty acid oxidation and HUFA synthesis pathways, and potentially important transcription factors, peroxisome proliferators activated receptors (PPARs), determined in selected tissues. Liver HUFA synthesis and desaturase gene expression was increased by dietary CLA and decreased by high dietary oil content. Carnitine palmitoyltransferase-I (CPT-I) activity and gene expression were generally increased by CLA in muscle tissues although dietary oil content had relatively little effect. In general CPT-I activity or gene expression was not correlated with β-oxidation. Dietary CLA tended to increase PPARα and β gene expression in both liver and muscle tissues, and PPARγ in liver. In summary, gene expression and activity of the fatty acid pathways were altered in response to dietary CLA and/or oil content, with data suggesting that PPARs are also regulated in response to CLA. Correlations were observed between dietary CLA, liver HUFA synthesis and desaturase gene expression, and liver PPARα expression, and also between dietary CLA, CPT-I expression and activity, and PPARα expression in muscle tissues. In conclusion, this study suggests that dietary CLA has effects on fatty acid metabolism in Atlantic salmon and on PPAR transcription factors. However, further work is required to assess the potential of CLA as a dietary supplement, and the role of PPARs in the regulation of lipid metabolism in fish

Excision of HIV-1 Proviral DNA by Recombinant Cell Permeable Tre-Recombinase

Over the previous years, comprehensive studies on antiretroviral drugs resulted in the successful introduction of highly active antiretroviral therapy (HAART) into clinical practice for treatment of HIV/AIDS. However, there is still need for new therapeutic approaches, since HAART cannot eradicate HIV-1 from the infected organism and, unfortunately, can be associated with long-term toxicity and the development of drug resistance. In contrast, novel gene therapy strategies may have the potential to reverse the infection by eradicating HIV-1. For example, expression of long terminal repeat (LTR)-specific recombinase (Tre-recombinase) has been shown to result in chromosomal excision of proviral DNA and, in consequence, in the eradication of HIV-1 from infected cell cultures. However, the delivery of Tre-recombinase currently depends on the genetic manipulation of target cells, a process that is complicating such therapeutic approaches and, thus, might be undesirable in a clinical setting. In this report we demonstrate that E.coli expressed Tre-recombinases, tagged either with the protein transduction domain (PTD) from the HIV-1 Tat trans-activator or the translocation motif (TLM) of the Hepatitis B virus PreS2 protein, were able to translocate efficiently into cells and showed significant recombination activity on HIV-1 LTR sequences. Tre activity was observed using episomal and stable integrated reporter constructs in transfected HeLa cells. Furthermore, the TLM-tagged enzyme was able to excise the full-length proviral DNA from chromosomal integration sites of HIV-1-infected HeLa and CEM-SS cells. The presented data confirm Tre-recombinase activity on integrated HIV-1 and provide the basis for the non-genetic transient application of engineered recombinases, which may be a valuable component of future HIV eradication strategies

A Conversation Among the IAS-USA Board of Directors: Hot Topics and Emerging Data in HIV Research and Care.

The IAS-USA volunteer Board of Directors met in October 2016 for its annual meeting. For the second year, the Board conducted a live, hour-long, interactive, roundtable webinar covering current questions and issues in HIV research, prevention, and care. Important highlights from the Board's discussion, which was moderated by Paul A. Volberding, MD, are included below. Members of the IAS-USA volunteer Board of Directors are Constance A. Benson, MD; Judith S. Currier, MD; Carlos del Rio, MD; Joel E. Gallant, MD, MPH; Roy M. Gulick, MD, MPH; Jeanne M. Marrazzo, MD, MPH; Douglas D. Richman, MD; Michael S. Saag, MD; Robert T. Schooley, MD; and Paul A. Volberding, MD

A Conversation Among the IAS-USA Board of Directors: Hot Topics and Emerging Data in HIV Research and Care.

The IAS-USA volunteer Board of Directors met in October 2016 for its annual meeting. For the second year, the Board conducted a live, hour-long, interactive, roundtable webinar covering current questions and issues in HIV research, prevention, and care. Important highlights from the Board's discussion, which was moderated by Paul A. Volberding, MD, are included below. Members of the IAS-USA volunteer Board of Directors are Constance A. Benson, MD; Judith S. Currier, MD; Carlos del Rio, MD; Joel E. Gallant, MD, MPH; Roy M. Gulick, MD, MPH; Jeanne M. Marrazzo, MD, MPH; Douglas D. Richman, MD; Michael S. Saag, MD; Robert T. Schooley, MD; and Paul A. Volberding, MD

What Science Says is Best': Parenting Practices, Scientific Authority and Maternal Identity.

Based on research in London with mothers from a breastfeeding support organisation this paper explores the narratives of women who breastfeed 'to full term' (typically for a period of several years) as part of a philosophy of 'attachment parenting', an approach to parenting which validates long term proximity between child and care-taker. In line with wider cultural trends, one of the most prominent 'accountability strategies' used by this group of mothers to explain their long-term breastfeeding is recourse to scientific evidence, both about the nutritional benefits of breastfeeding and about the broader cognitive and developmental benefits of attachment parenting more broadly. Women's accounts internalize and reflect popular literature around attachment parenting, which is explored here in-depth as a means of contextualizing shifting patterns of 'scientisation'. What follows is a reflection on how 'scientific evidence' is given credence in narratives of mothering, and what the implications of this are for individuals in their experience of parenting, and for society more broadly. As a form of 'Authoritative Knowledge' (Jordan 1997) women utilise 'science' when they talk about their decisions to breastfeed long-term, since it has the effect of placing these non-conventional practices beyond debate (they are simply what is 'healthiest'). The article therefore makes a contribution to wider sociological debates around the ways in which society and behaviour are regulated, and the ways in which 'science' is interpreted, internalized and mobilized by individuals in the course of their 'identity work'