Aerothermodynamic Analyses of Towed Ballutes

A ballute (balloon-parachute) is an inflatable, aerodynamic drag device for application to planetary entry vehicles. Two challenging aspects of aerothermal simulation of towed ballutes are considered. The first challenge, simulation of a complete system including inflatable tethers and a trailing toroidal ballute, is addressed using the unstructured-grid, Navier-Stokes solver FUN3D. Auxiliary simulations of a semi-infinite cylinder using the rarefied flow, Direct Simulation Monte Carlo solver, DSV2, provide additional insight into limiting behavior of the aerothermal environment around tethers directly exposed to the free stream. Simulations reveal pressures higher than stagnation and corresponding large heating rates on the tether as it emerges from the spacecraft base flow and passes through the spacecraft bow shock. The footprint of the tether shock on the toroidal ballute is also subject to heating amplification. Design options to accommodate or reduce these environments are discussed. The second challenge addresses time-accurate simulation to detect the onset of unsteady flow interactions as a function of geometry and Reynolds number. Video of unsteady interactions measured in the Langley Aerothermodynamic Laboratory 20-Inch Mach 6 Air Tunnel and CFD simulations using the structured grid, Navier-Stokes solver LAURA are compared for flow over a rigid spacecraft-sting-toroid system. The experimental data provides qualitative information on the amplitude and onset of unsteady motion which is captured in the numerical simulations. The presence of severe unsteady fluid - structure interactions is undesirable and numerical simulation must be able to predict the onset of such motion

Human CCS gene: genomic organization and exclusion as a candidate for amyotrophic lateral sclerosis (ALS)

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive lethal disorder of large motor neurons of the spinal cord and brain. In approximately 20% of the familial and 2% of sporadic cases the disease is due to a defect in the gene encoding the cytosolic antioxidant enzyme Cu, Zn-superoxide dismutase (SOD1). The underlying molecular defect is known only in a very small portion of the remaining cases and therefore involvement of other genes is likely. As SOD1 receives copper, essential for its normal function, by the copper chaperone, CCS (Copper Chaperone for SOD), we considered CCS as a potential candidate gene for ALS. RESULTS: We have characterized the genomic organization of CCS and determined exon-intron boundaries. The 823 bp coding region of the CCS is organized in 8 exons. We have evaluated involvement of the CCS in ALS by sequencing the entire coding region for mutations in 20 sporadic ALS patients. CONCLUSIONS: No causative mutations for the ALS have been detected in the CCS gene in 20 sporadic ALS patients analyzed, but an intragenic single nucleotide polymorphism has been identified

Substantial Intestinal Microbiota Differences Between Patients With Ulcerative Colitis From Ghana and Denmark:Ulcerative Colitis in Denmark vs Ghana

BACKGROUND: Ulcerative colitis (UC) is a relapsing nontransmural inflammatory disease that is restricted to the colon and is characterized by flare-ups of bloody diarrhea. In this study, we aimed to investigate intestinal bacterial diversity in healthy controls and patients with UC with and without active disease, from Ghana and Denmark. METHODS: The study included 18 UC patients (9 with active and 9 with inactive disease) and 18 healthy controls from Ghana. In addition 16 UC patients from Denmark (8 UC with active and 8 UC with inactive disease) and 19 healthy controls from Denmark. Microbiota diversity analysis relied on sequencing of ribosomal small subunit genes. Purified genomic DNA was submitted to PCR using a primer set targeting prokaryotes and eukaryotes. The purified DNA was sequenced on the Illumina MiSeq system in a 2 × 250 bp set up (Illumina, San Diego, CA, USA). Blinded analysis of the taxonomy table was performed using BioNumerics-7.5 (Applied Maths NV, Sint-Martens-Latem, Belgium). RESULTS: When analyzing the taxonomy data for prokaryotes, cluster and principal component analysis shows Danish healthy controls clustered together, but separate from healthy controls from Ghana, which also clustered together. The Shannon diversity index (SDI) for prokaryotes shows significant differences between Danish healthy controls and patients in comparison with the corresponding groups from Ghana (p = 0.0056). Significant increased abundance of Escherichia coli was detected in healthy controls from Ghana in comparison with healthy controls from Denmark. The SDI of the prokaryotes ranges between 0 and 3.1 in the Ghana study groups, while in the Danish study groups it ranges between 1.4 and 3.2, the difference is however not significant (p = 0.138). Our data show a significant increased abundance of eukaryotes species in the healthy control group from Ghana and Denmark in comparison with patient groups from Ghana and Denmark. CONCLUSION: Overall, healthy controls and patients with UC from Denmark have increased diversity of prokaryotes. Healthy controls from Denmark and Ghana have increased abundance of eukaryotes in comparison with UC patient groups from Denmark and Ghana

DNA Damage Repair and Drug Efflux as Potential Targets for Reversing Low or Intermediate Ciprofloxacin Resistance in E. coli K-12

Ciprofloxacin is a potent antibacterial drug that is widely used in human clinical applications. As a consequence of its extensive use, resistance has emerged in almost all clinically relevant bacterial species. A mean to combat the observed ciprofloxacin resistance is by reversing it via co-administration of a potentiating compound, also known as a helper drug. Here, we report on the current advances in identifying ciprofloxacin helper drugs, and put them into perspective of our own findings. We searched for potential helper drug targets in Escherichia coli strains with different levels of ciprofloxacin resistance using transcriptomics i.e., RNAseq and by deletion of genes associated with hyper-susceptibility to ciprofloxacin. Differential gene expression analysis of the highly ciprofloxacin resistant uropathogenic E. coli strain, ST131 UR40, treated with a clinically relevant concentration of ciprofloxacin (2 μg/mL), showed that the transcriptome was unaffected. Conversely, genetic screening of 23 single gene deletions in the high-level ciprofloxacin resistant laboratory derived E. coli strain, LM693, led to a significant decrease in the minimal inhibitory concentration for several genes, including genes encoding the AcrAB-TolC efflux pump, SOS-response proteins and the global regulator Fis. In addition, deletion of acrA, tolC, recA, or recC rendered two E. coli strains with intermediate susceptibility to ciprofloxacin fully susceptible according to the CLSI recommended breakpoint. Our results corroborate the AcrAB-TolC efflux pump and the SOS response proteins, RecA and RecC, as potential targets for ciprofloxacin helper drugs in treatment of human bacterial infections caused by E. coli strains with intermediate sensitivity to ciprofloxacin

Targeting endogenous retroviruses using a novel adenoviral vaccine technology

Human Endogenous Retroviruses (HERVs) are promising cancer vaccine targets as they are reactivated in cancers while being silent in healthy tissues. Around 8-9% of our genome is made up of HERVs and reactivation of HERVs, especially HERV-K, have been implicated in tumorigenesis via oncogenic signaling and immune evasion. As one of the means for cancer immune evasion, HERVs utilize an Immune Suppressive Domain (ISD) located in their envelope protein (Env). Here, our cancer vaccine strategy was to evaluate if adenoviral vaccines encoding a virus-like particle immunogen design including Gag for particle formation and an ISD mutated Env protein (ISDmut) as a surface target, could induce potent and efficacious immune responses. For this purpose, we used the adenoviral vectors hAd19a and hAd5. Please click Download on the upper right corner to see the full abstract

Individual variation in levels of haptoglobin-related protein in children from Gabon

Background: Haptoglobin related protein (Hpr) is a key component of trypanosome lytic factors (TLF), a subset of highdensity lipoproteins (HDL) that form the first line of human defence against African trypanosomes. Hpr, like haptoglobin (Hp) can bind to hemoglobin (Hb) and it is the Hpr-Hb complexes which bind to these parasites allowing uptake of TLF. This unique form of innate immunity is primate-specific. To date, there have been no population studies of plasma levels of Hpr, particularly in relation to hemolysis and a high prevalence of ahaptoglobinemia as found in malaria endemic areas. Methods and Principal Findings: We developed a specific enzyme-linked immunosorbent assay to measure levels of plasma Hpr in Gabonese children sampled during a period of seasonal malaria transmission when acute phase responses (APR), malaria infection and associated hemolysis were prevalent. Median Hpr concentration was 0.28 mg/ml (range 0.03-1.1). This was 5-fold higher than that found in Caucasian children (0.049 mg/ml, range 0.002-0.26) with no evidence of an APR. A general linear model was used to investigate associations between Hpr levels, host polymorphisms, parasitological factors and the acute phase proteins, Hp, C-reactive protein (CRP) and albumin. Levels of Hpr were associated with Hp genotype, decreased with age and were higher in females. Hpr concentration was strongly correlated with that of Hp, but not CRP

A Robust Determination of the Time Delay in 0957+561A,B and a Measurement of the Global Value of Hubble's Constant

Photometric monitoring of the gravitational lens system 0957+561A,B in the g and r bands with the Apache Point Observatory (APO) 3.5 m telescope during 1996 shows a sharp g band event in the trailing (B) image light curve at the precise time predicted from the observation of an event during 1995 in the leading (A) image with a delay of 415 days. This success confirms the "short delay," and the lack of any feature at a delay near 540 days rejects the "long delay" for this system, resolving a long-standing controversy. A series of statistical analyses of our light curve data yield a best fit delay of 417 +/- 3 days (95% confidence interval). Recent improvements in the modeling of the lens system (consisting of a galaxy and cluster) allow us to derive a value of the global (at z = 0.36) value of Hubble's constant H_0 using Refsdal's method, a simple and direct distance determination based on securely understood physics and geometry. The result is H_0 = 63 +/- 12 km/s/Mpc (for Omega = 1) where this 95% confidence interval is dominated by remaining lens model uncertainties.Comment: accepted by ApJ, AASTeX 4.0 preprint, 4 PostScript figure

TESS Discovery of an ultra-short-period planet around the nearby M dwarf LHS 3844

Data from the newly-commissioned \textit{Transiting Exoplanet Survey Satellite} (TESS) has revealed a "hot Earth" around LHS 3844, an M dwarf located 15 pc away. The planet has a radius of $1.32\pm 0.02$ $R_\oplus$ and orbits the star every 11 hours. Although the existence of an atmosphere around such a strongly irradiated planet is questionable, the star is bright enough ($I=11.9$, $K=9.1$) for this possibility to be investigated with transit and occultation spectroscopy. The star's brightness and the planet's short period will also facilitate the measurement of the planet's mass through Doppler spectroscopy.Comment: 10 pages, 4 figures. Submitted to ApJ Letters. This letter makes use of the TESS Alert data, which is currently in a beta test phase, using data from the pipelines at the TESS Science Office and at the TESS Science Processing Operations Cente