DNS in Computer Forensics

The Domain Name Service (DNS) is a critical core component of the global Internet and integral to the majority of corporate intranets. It provides resolution services between the human-readable name-based system addresses and the machine operable Internet Protocol (IP) based addresses required for creating network level connections. Whilst structured as a globally dispersed resilient tree data structure, from the Global and Country Code Top Level Domains (gTLD/ccTLD) down to the individual site and system leaf nodes, it is highly resilient although vulnerable to various attacks, exploits and systematic failures

Overview of the MEDLI Project

The Mars Science Laboratory Entry, Descent, and Landing Instrumentation (MEDLI) Project s objectives are to measure aerothermal environments, sub-surface heatshield material response, vehicle orientation, and atmospheric density for the atmospheric entry and descent phases of the Mars Science Laboratory (MSL) entry vehicle. The flight science objectives of MEDLI directly address the largest uncertainties in the ability to design and validate a robust Mars entry system, including aerothermal, aerodynamic and atmosphere models, and thermal protection system (TPS) design. The instrumentation suite will be installed in the heatshield of the MSL entry vehicle. The acquired data will support future Mars entry and aerocapture missions by providing measured atmospheric data to validate Mars atmosphere models and clarify the design margins for future Mars missions. MEDLI thermocouple and recession sensor data will significantly improve the understanding of aeroheating and TPS performance uncertainties for future missions. MEDLI pressure data will permit more accurate trajectory reconstruction, as well as separation of aerodynamic and atmospheric uncertainties in the hypersonic and supersonic regimes. This paper provides an overview of the project including the instrumentation design, system architecture, and expected measurement response

Long-term multi-wavelength studies of GRS 1915+105 I. A high-energy and mid-infrared focus with RXTE, INTEGRAL, and Spitzer

To date, mid-infrared properties of Galactic black hole binaries have barely been investigated in the framework of multi-wavelength campaigns. Yet, studies in this spectral domain are crucial to get complementary information on the presence of dust and/or on the physical processes such as dust heating and thermal bremsstrahlung. Here, we report a long-term multi-wavelength study of the microquasar GRS 1915+105. On the one hand, we aimed at understanding the origins of the mid-infrared emission, and on the other hand, at searching for correlation with the high-energy and/or radio activities. We observed the source at several epochs between 2004 and 2006 with the photometer IRAC and spectrometer IRS, both mounted on the Spitzer Space Telescope. When available, we completed our set of data with quasi-simultaneous RXTE and INTEGRAL high-energy and/or Ryle radio observations from public archives. We then studied the mid-infrared environment and activities of GRS 1915+105 through spectral analysis and broad band fitting of its radio to X-ray spectral energy distributions. We detected polycyclic aromatic hydrocarbon molecules in all but one IRS spectra of GRS 1915+105 which unambiguously proves the presence of a dust component, likely photoionised by the high-energy emission. We also argue that this dust is distributed in a disc-like structure heated by the companion star, as observed in some Herbig Ae/Be and isolated cool giant stars. Moreover, we show that some of the soft X-ray emission emanating from the inner regions of the accretion disc is reprocessed and thermalised in the outer part. This leads to a mid-infrared excess that is very likely correlated to the soft X-ray emission. We exclude thermal bremsstrahlung as contributing significantly in this spectral domain.Comment: 46 pages, 6 tables, 6 figures, accepted in Ap

Dexfenfluramine and the oestrogen-metabolizing enzyme CYP1B1 in the development of pulmonary arterial hypertension

<p>Aims: Pulmonary arterial hypertension (PAH) occurs more frequently in women than men. Oestrogen and the oestrogen-metabolising enzyme cytochrome P450 1B1 (CYP1B1) play a role in the development of PAH. Anorectic drugs such as dexfenfluramine (Dfen) have been associated with the development of PAH. Dfen mediates PAH via a serotonergic mechanism and we have shown serotonin to up-regulate expression of CYP1B1 in human pulmonary artery smooth muscle cells (PASMCs). Thus here we assess the role of CYP1B1 in the development of Dfen-induced PAH.</p> <p>Methods and results: Dfen (5 mg kg−1 day−1 PO for 28 days) increased right ventricular pressure and pulmonary vascular remodelling in female mice only. Mice dosed with Dfen showed increased whole lung expression of CYP1B1 and Dfen-induced PAH was ablated in CYP1B1−/− mice. In line with this, Dfen up-regulated expression of CYP1B1 in PASMCs from PAH patients (PAH-PASMCs) and Dfen-mediated proliferation of PAH-PASMCs was ablated by pharmacological inhibition of CYP1B1. Dfen increased expression of tryptophan hydroxylase 1 (Tph1; the rate-limiting enzyme in the synthesis of serotonin) in PAH-PASMCs and both Dfen-induced proliferation and Dfen-induced up-regulation of CYP1B1 were ablated by inhibition of Tph1. 17β-Oestradiol increased expression of both Tph1 and CYP1B1 in PAH-PASMCs, and Dfen and 17β-oestradiol had synergistic effects on proliferation of PAH-PASMCs. Finally, ovariectomy protected against Dfen-induced PAH in female mice.</p> <p>Conclusion: CYP1B1 is critical in the development of Dfen-induced PAH in mice in vivo and proliferation of PAH-PASMCs in vitro. CYP1B1 may provide a novel therapeutic target for PAH.</p&gt

Processing of Chlamydia abortus polymorphic membrane protein 18D during the chlamydial developmental cycle

BACKGROUND: Chlamydia possess a unique family of autotransporter proteins known as the Polymorphic membrane proteins (Pmps). While the total number of pmp genes varies between Chlamydia species, all encode a single pmpD gene. In both Chlamydia trachomatis (C. trachomatis) and C. pneumoniae, the PmpD protein is proteolytically cleaved on the cell surface. The current study was carried out to determine the cleavage patterns of the PmpD protein in the animal pathogen C. abortus (termed Pmp18D). METHODOLOGY/PRINCIPAL FINDINGS: Using antibodies directed against different regions of Pmp18D, proteomic techniques revealed that the mature protein was cleaved on the cell surface, resulting in a100 kDa N-terminal product and a 60 kDa carboxy-terminal protein. The N-terminal protein was further processed into 84, 76 and 73 kDa products. Clustering analysis resolved PmpD proteins into three distinct clades with C. abortus Pmp18D, being most similar to those originating from C. psittaci, C. felis and C. caviae. CONCLUSIONS/SIGNIFICANCE: This study indicates that C. abortus Pmp18D is proteolytically processed at the cell surface similar to the proteins of C. trachomatis and C. pneumoniae. However, patterns of cleavage are species-specific, with low sequence conservation of PmpD across the genus. The absence of conserved domains indicates that the function of the PmpD molecule in chlamydia remains to be elucidated

Anti-plasmodial polyvalent interactions in Artemisia annua L. aqueous extract – possible synergistic and resistance mechanisms

Artemisia annua hot water infusion (tea) has been used in in vitro experiments against P. falciparum malaria parasites to test potency relative to equivalent pure artemisinin. High performance liquid chromatography (HPLC) and mass spectrometric analyses were employed to determine the metabolite profile of tea including the concentrations of artemisinin (47.5±0.8 mg L-1), dihydroartemisinic acid (70.0±0.3 mg L-1), arteannuin B (1.3±0.0 mg L-1), isovitexin (105.0±7.2 mg L-1) and a range of polyphenolic acids. The tea extract, purified compounds from the extract, and the combination of artemisinin with the purified compounds were tested against chloroquine sensitive and chloroquine resistant strains of P. falciparum using the DNA-intercalative SYBR Green I assay. The results of these in vitro tests and of isobologram analyses of combination effects showed mild to strong antagonistic interactions between artemisinin and the compounds (9-epi-artemisinin and artemisitene) extracted from A. annua with significant (IC50 <1 μM) anti-plasmodial activities for the combination range evaluated. Mono-caffeoylquinic acids, tri-caffeoylquinic acid, artemisinic acid and arteannuin B showed additive interaction while rosmarinic acid showed synergistic interaction with artemisinin in the chloroquine sensitive strain at a combination ratio of 1:3 (artemisinin to purified compound). In the chloroquine resistant parasite, using the same ratio, these compounds strongly antagonised artemisinin anti-plasmodial activity with the exception of arteannuin B, which was synergistic. This result would suggest a mechanism targeting parasite resistance defenses for arteannuin B’s potentiation of artemisinin

A Magnetohydrodynamic enhanced entry system for space transportation: MEESST

This paper outlines the initial development of a novel magnetohydrodynamic (MHD) plasma control system which aims at mitigating shock-induced heating and the radio-frequency communication blackout typically encountered during (re-)entry into planetary atmospheres. An international consortium comprising universities, SMEs, research institutions, and industry has been formed in order to develop this technology within the MEESST project. The latter is funded by the Future and Emerging Technologies (FET) program of the European Commission’s Horizon 2020 scheme (grant no. 899298). Atmospheric entry imposes one of the harshest environments which a spacecraft can experience. The combination of hypersonic velocities and the rapid compression of atmospheric particles by the spacecraft leads to high-enthalpy, partially ionised gases forming around the vehicle. This inhibits radio communications and induces high thermal loads on the spacecraft surface. For the former problem, spacecraft can sometimes rely on satellite constellations for communicating through the plasma wake and therefore preventing the blackout. On the other hand, expensive, heavy, and non-reusable thermal protection systems (TPS) are needed to dissipate the severe thermal loads. Such TPS can represent up to 30% of an entry vehicles weight, and especially for manned missions they can reduce the cost- efficiency by sacrificing payload mass. Such systems are also prone to failure, putting the lives of astronauts at risk. The use of electromagnetic fields to exploit MHD principles has long been considered as an attractive solution for tackling the problems described above. By pushing the boundary layer of the ionized gas layer away from the spacecraft, the thermal loads can be reduced, while also opening a magnetic window for radio communications and mitigating the blackout phenomenon. The application of this MHD-enabled system has previously not been demonstrated in realistic conditions due to the required large magnetic fields (on the order of Tesla or more), which for conventional technologies would demand exceptionally heavy and power-hungry electromagnets. High-temperature superconductors (HTS) have reached a level of industrial maturity sufficient for them to act as a key enabling technology for this application. Thanks to superior current densities, HTS coils can offer the necessary low weight and compactness required for space applications, with the ability to generate the strong magnetic fields needed for entry purposes. This paper provides an overview of the MEESST project, including its goals, methodology and some preliminary design considerations

The Uptake and Accuracy of Oral Kits for HIV Self-Testing in High HIV Prevalence Setting: A Cross-Sectional Feasibility Study in Blantyre, Malawi

Augustine Choko and colleagues assess the uptake and acceptability of home-based supervised oral HIV self-testing in Malawi, demonstrating the feasibility of this approach in a high-prevalence, low-income environment

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.